non-invasive method of diagnosing Parkinson’s disease early using an eye scan It could mean treatment aimed at slowing the disease can start sooner or could be used to monitor the disease’s progression As is the case with many progressive conditions the earlier that Parkinson’s disease is diagnosed Early diagnosis means that interventions can be introduced ahead of time that may prevent or curtail the disease’s destructive course most Parkinson’s diagnoses are made after the emergence of symptoms Researchers from Université Laval and its affiliate, the CERVO Brain Research Center have developed a method of diagnosing Parkinson’s disease (PD) early “By [the time symptoms appear], the disease has been present for several years and the affected neurons are already engaged in an irreversible degenerative process,” said the study’s corresponding author, Martin Lévesque, PhD professor at Laval’s Faculty of Medicine and CERVO researcher “That’s why it’s important to find biomarkers that detect Parkinson’s at an early stage of the disease An unusual response of the retina to light stimuli could be indicative of a pathology affecting the brain.” In recent years, visual impairments arising from retinal dysfunction have gained attention as potential indicators of PD Electroretinography (ERG) is a technique used to evaluate the electrical activity of the retina the light-sensitive tissue at the back of the eye A device delivers light flashes or patterns to the eye and electrodes placed on and around the eye measure the electrical responses generated by different types of retinal cells to give insight into how well they are functioning While ERG has been used to reveal subtle retinal changes that correlate with psychiatric disorders such as schizophrenia its use has not been widely researched in the setting of PD the researchers hypothesized that distinct ERG impairments could serve as early Parkinson’s indicators They tested their hypothesis on 20 adults who had been diagnosed with PD within the last five years “We placed an electrode on each participant’s lower eyelid and recorded their retinal response to a series of flashes of different intensity “We did the same with people of the same age The results we obtained for people with Parkinson’s had a distinct signature from those in the control group.” The researchers also used ERG to test their theory on two-month-old M83 transgenic mice, genetically engineered to produce a mutated form of the human alpha-synuclein protein associated with familial forms of PD M83 mice develop motor impairments and neurological symptoms like those seen in human patients with Parkinson’s The results of ERG testing on these mice were compared with those of an age-matched control group “We used young mice in which no motor signs of the disease were yet observable,” said Lévesque we obtained different responses in Parkinson’s model animals This suggests that the functional manifestations of Parkinson’s could be detected at an early stage of the disease by retinal examination.” The average age of Parkinson’s diagnosis is 65 The researchers hope that this simple and non-invasive test can be used to start diagnosing PD earlier it can be used to keep an eye on the disease’s progression “We could offer a functional retinal exam from the age of 50,” Lévesque said we could offer interventions that prevent the degeneration of the neurons involved in Parkinson’s This approach could also be used to monitor the progression of the disease as well as the effectiveness of interventions offered to patients.” The study was published in the journal Neurobiology of Disease Source: Université Laval, EurekAlert! mark the first time a psychedelic has been tested in people with any neurodegenerative disease Parkinson’s disease is best known for its motor symptoms But many people with the disease also struggle with depression and anxiety which often begin years before motor symptoms appear These mood issues are not just emotionally distressing—they are strongly linked to faster physical decline and worse overall quality of life Standard treatments for depression and anxiety are often less effective in people with Parkinson’s making the search for new therapeutic options especially urgent Psilocybin is a naturally occurring psychedelic compound that is converted in the body into psilocin which interacts with serotonin receptors in the brain Studies in major depression and anxiety linked to terminal illness have shown that even a single dose of psilocybin can lead to rapid and long-lasting improvements in mood Scientists believe the drug may help the brain form new neural connections These effects may be particularly relevant for people with Parkinson’s disease and loss of neural connectivity—all factors that may contribute to both mood and motor symptoms Given the complex neurobiology of Parkinson’s and concerns about possible drug interactions and psychosis risk the research team at the University of California San Francisco set out to test the safety and tolerability of psilocybin in this population They enrolled 12 participants between the ages of 40 and 75 all of whom had mild to moderate Parkinson’s disease and met diagnostic criteria for depression or anxiety People with significant cognitive impairment or other medical risks were excluded from the trial Most participants were already being treated with levodopa the most common medication for managing motor symptoms of Parkinson’s Each participant underwent two supervised psilocybin sessions on a research unit at UCSF followed about two weeks later by a higher Both sessions were paired with multiple psychotherapy visits before and after the researchers used a range of assessments These included standard clinical rating scales for motor and non-motor Parkinson’s symptoms Safety was monitored throughout the sessions and reports of any adverse psychological or physical effects The study found that psilocybin was generally well tolerated The most common side effects during the sessions included mild anxiety and temporary increases in heart rate or blood pressure Two participants reported intense anxiety during one of the sessions and one of them experienced a transient worsening of tremor and increased thoughts about death related to future disability and suicidal ideation decreased overall after treatment the researchers observed a range of improvements across different symptom domains Participants reported significant reductions in depression and anxiety one week after the high-dose session and these gains were maintained at the three-month follow-up as measured by both self-reports and clinician ratings These included reductions in everyday motor difficulties and improvements in motor exam scores The magnitude of these improvements exceeded thresholds considered clinically meaningful Cognitive function also improved in several domains Participants performed better on tests of memory These gains were still present a month after the psilocybin session caregiver reports also reflected meaningful changes Family members noted that participants were less distressed by neuropsychiatric symptoms and showed fewer behavioral issues They also expressed high satisfaction with the treatment While the improvements in mood were expected based on prior research in depression the benefits in motor symptoms and cognition were unexpected The authors suggest several possible explanations One is that psilocybin may directly influence dopamine and serotonin signaling in ways that support motor control Another is that improving mood may indirectly benefit motor function as depression is associated with increased stress and biological changes that can worsen physical symptoms A third possibility is that psilocybin may influence the underlying disease process through its effects on inflammation or other brain systems disrupted in Parkinson’s “We are still in very early stages of this work but this first study went well beyond what we expected,” said the paper’s first author an assistant professor and associate director of UCSF’s Translational Psychedelic Research Program (TrPR) but mood symptoms in Parkinson’s are linked to a faster physical decline And they are actually a stronger predictor of patients’ quality of life with Parkinson’s than their motor symptoms.” With only 12 participants and no placebo group the findings must be interpreted with caution Expectancy effects and the powerful psychological context of the therapy sessions may have contributed to the observed improvements because the study excluded people with more advanced disease or significant medical complications it’s unclear how generalizable the results are Future research will need to include more diverse and larger samples to better understand the risks and benefits Encouraged by the results of this pilot study the researchers have launched a larger randomized controlled trial involving 100 participants across two sites: UCSF and Yale University This follow-up study will include brain imaging and blood tests to help identify how psilocybin affects the brain and immune system The hope is to uncover biological mechanisms behind the clinical improvements and determine whether psilocybin could one day become part of Parkinson’s care “The vast majority of brain diseases still lack interventions that change the course of illness,” said the study’s senior author an associate professor at UCSF and director of the TrPR Program but we don’t alter the trajectory or prevent decline These results raise the exciting possibility that psilocybin may help the brain repair itself.” A study of British adults found that those who had used psychedelics were 25% less likely to report frequent bad headaches, adding to growing research on psychedelics’ potential medical benefits. Does psilocybin affect everyone the same way? New research suggests that race and ethnicity may play a role in the long-term benefits of this psychedelic substance. A single dose of psilocybin significantly increased emotional empathy in depressed individuals for up to two weeks. Feelings of shame and guilt are surprisingly common during psilocybin experiences, affecting most users. However, a new study reveals that constructively working through these emotions, rather than avoiding them, is linked to improved wellbeing afterward. Dancing can significantly reduce depression in Parkinson's disease, a new study suggests. Not only did participants report feeling better, but brain scans also showed decreased activity in a key area linked to emotional regulation. A study found that levodopa-induced dyskinesia disconnects the motor cortex from movement control, allowing abnormal movements. Ketamine reduced these movements, restored some brain control, and altered neural interactions, showing promise as a potential treatment. Consuming unsweetened caffeinated coffee is linked to a lower risk of Alzheimer’s, Parkinson’s, and related mortality, while sweetened or artificially sweetened coffee showed no such benefits. Please enter your username or email address to reset your password. Please call us on 1800 070 535 and we’ll help resolve the issue or try again later Any Questions? Please call 1800 070 535 Saturday & Sunday 7:00am – 11:30am (AEST) Mounting evidence suggests there might be two separate types of the world’s fastest-growing neurological condition Can this fresh understanding lead to much-needed new treatments By Alexandra Thompson Per Borghammer’s “aha” moment came nearly 20 years ago The neuroscientist was reading a paper from researchers who were examining whether REM sleep behaviour disorder (RBD) a condition that causes people to act out their dreams and is often found in people who later develop Parkinson’s disease could be an early form of the neurological condition Rather than starting with the brain, however, the team instead looked for nerve cell loss in the heart. Though Parkinson’s is historically associated with nerve cell depletion in the brain, it also affects neurons in the heart that manage autonomic functions such as heart rate and blood pressure. And, says Borghammer the heart is invisible; it is gone.” Not literally, of course. But in these people, the neurons that produce the neurotransmitter norepinephrine, which helps control heart rate, were so depleted that their hearts didn’t show up on scans using radioactive tracers. This kind of neuron loss is associated with Parkinson’s none of the people had been diagnosed with the disease and their brain scans seemed normal Read more What struck Borghammer was that Parkinson’s didn’t seem to follow the same trajectory in everyone it affected: RBD strongly predicts Parkinson’s, but not everyone with Parkinson’s experiences RBD “I realised that Parkinson’s must be at least two types,” says Borghammer – when neuron loss starts outside the brain, eventually working its way in, and when neuron loss is largely restricted to the brain from the beginning Sarah DeWeerdt is a science journalist in Seattle Throughout 2021 and 2022, researchers at Ghent University Hospital in Belgium watched with cautious optimism as nearly 50 people with early stage Parkinson’s disease visited the clinic as part of a trial of a potential treatment1 Everyday tasks had become difficult for these participants some of them seemed to be returning for follow-up appointments with a new lease of life they were less stiff,” says study co-leader Patrick Santens “They were having less trouble in their daily functioning Nature Outlook: The human microbiome the researchers checked which of the volunteers had received the treatment and which had instead been given a placebo the scientists found that participants’ scores on a widely used test of motor function had improved by an average of almost six points — a result that exceeded expectations Trials of treatments for Parkinson’s disease often show improvements of two or three points on the movement scale but that doesn’t make a meaningful difference in people’s lives “It’s quite something when you can achieve that.” The nature of the treatment being tested was also a little surprising It was not a high-tech designer drug with a price tag to match but rather a one-time delivery of gut microorganisms from healthy donors into the digestive tract of people with Parkinson’s disease Although faecal microbiota transplantation (FMT) has become widely accepted for the treatment of recurrent gut infections of harmful bacteria its use for what is typically thought of as a brain condition is more unexpected More research will be necessary to confirm the results and clarify who is most likely to benefit from the procedure and which microbes are most crucial to the treatment’s success This knowledge could contribute to efforts already under way to develop small-molecule drugs that target pathways linking the disease to the gut But even as opportunities for treatment begin to be revealed scientists still don’t have a clear picture of how — or even whether — the gut microbiome actually contributes to Parkinson’s pathology Parkinson’s disease affects nearly 3% of people over the age of 65 globally Its characteristic movement difficulties stem from a loss of neurons in a part of the brain called the substantia nigra pars compacta These neurons typically release the signalling molecule dopamine and current treatments such as levodopa aim to alleviate Parkinson’s symptoms by replacing lost dopamine in the brain Yet the disease is not confined to the brain; a link to the gut has long been known experience constipation and trouble with food moving from the stomach to the small intestine One-quarter of people with Parkinson’s also have a condition called small-intestine bacterial overgrowth in which more bacteria than usual build-up inside the gut Several studies have looked for evidence of changes in the composition of the gut microbiome. In the largest such study so far, published in 2022, researchers gathered stool samples from 490 individuals with Parkinson’s disease and 234 healthy controls and sequenced the DNA of the microbes present 2 Researchers at Ghent University Hospital in Belgium prepare fluid for faecal transplantation in a trial to treat Parkinson’s disease people with Parkinson’s disease experience widespread changes to their gut microbiota “There are actually clusters — not individual microbes but clusters of microbes — that tend to grow together or be depleted together,” explains Haydeh Payami a geneticist at the University of Alabama at Birmingham Among the clusters are high levels of opportunistic pathogens microbes such as Escherichia coli and Klebsiella that do not typically cause harm but can do so when the microbiota as a whole is out of balance Species that digest dietary fibre and produce short-chain fatty acids — molecules that are known to be beneficial across many body systems — are severely depleted “There’s a lot of things that are going on,” says Payami But the significant question that this leaves open is the relationship between the gut symptoms and the motor symptoms of Parkinson’s disease “I do not know if the gut microbiome has anything to do with the pathology of Parkinson’s disease Or is the gut getting sick because the person is sick with Parkinson’s?” she asks In 2003, researchers led by neuroanatomist Heiko Braak proposed that Parkinson’s disease might be caused by an unknown pathogen that enters the body through the gastrointestinal tract and travels to the brain along the vagus nerve — the neural highway linking parts of the digestive tract to the central nervous system3 Their paper crystallized interest in the idea of a gut origin for Parkinson’s: after all it had long been known that some people have gut troubles years before developing the movement problems that trigger a Parkinson’s diagnosis which was once a common treatment for chronic heartburn Researchers have also found clumps of a protein called α-synuclein in gut neurons before the development of the disease (Cells in the appendix express especially high levels of α-synuclein which might explain why an appendectomy lowers risk.) Neurons in the gut make dopamine and oxidized dopamine — which can be produced by gut inflammation — triggers α-synuclein clumping Gut microbes themselves can produce molecules with a structure similar to α-synuclein These α-synuclein ‘mimics’ can also form clumps and might trigger clumping of α-synuclein itself “All of these molecules that are potentially involved in Parkinson’s disease are present in the gut,” says Elizabeth Bess, an organic chemist at the University of California, Irvine, who has investigated how chemical reactions performed by gut bacteria trigger α-synuclein clumping6 have been found in gut neurons.Credit: BIOLUTION GMBH / Science Photo Library the microbiota might hamper the effectiveness of Parkinson’s disease treatment: some bacteria are able to convert the drug levodopa into dopamine in the gut potentially reducing the dose delivered to the brain Suggestive though such findings might be, most researchers think that current evidence is not sufficient to say definitively whether alterations in the gut microbiome drive Parkinson’s disease in humans. Many suspect that there are multiple aetiologies, with some people experiencing ‘gut-first’ disease, and others ‘brain-first’ disease10 One reason why it is so difficult to untangle the causal relationships is that gut symptoms are fairly non-specific a neuroscientist at Duke University in Durham “There are lots of reasons why somebody might have gut dysbiosis and changes in their microbiome” she says Until we have a way to intervene to see if that’s going to reduce incidence of Parkinson’s up front it’s going to be hard to answer questions of cause and effect Geneticist Haydeh Payami at the University of Alabama at Birmingham found that people with Parkinson’s disease experience widespread changes to their gut microbiota.Credit: University of Alabama at Birmingham FMT studies have also yielded some puzzling surprises researchers found that people in the placebo group who received an infusion of their own gut microbiota improved by an average of 2.7 points on the movement scale Some other FMT trials have also suggested a placebo effect Santens is using the data from his trial to inform the design of a larger one that he and a group of colleagues aim to launch by early 2026 he is looking for bacterial species or other donor characteristics that correlate with treatment success there is no clear component or source of faecal material that seems necessary for success “There is no real ‘super donor’ effect,” he says signs that people with severe constipation benefit less from the transplant and would therefore not be the ideal target population includes people who harbour elevated levels of opportunistic pathogens whereas individuals in another lack fibre-fermenting bacteria About 20% of the group do not have a disrupted microbiota at all The analysis points the way towards using microbiota characteristics as a biomarker to guide treatment But treatments that aim to broadly alter the microbiota might not be the ultimate goal Some scientists are investigating the mechanisms underpinning the gut microbiota’s contribution to Parkinson’s disease with the aim of developing more targeted treatments we’ve thought that that makes it a better target for inhibiting disease processes,” says Bess But some scientists are questioning that view “An emerging perspective is that because it’s so malleable modulating the body’s response to gut microbiota activities might prove simpler and more durable Another team of researchers has zeroed in on a molecule produced by E. coli called curli — an α-synuclein mimic that, in mice, is also associated with Parkinson’s-like pathology in the brain17 The researchers also demonstrated that a molecule derived from green tea can dampen curli’s effect on α-synuclein aggregation co-founded by study team member and microbiologist Sarkis Mazmanian at the California Institute of Technology in Pasadena is now developing a drug based on this molecule Other researchers are working to fill in the bigger picture much of the research on microbiome changes in Parkinson’s disease consists of “snapshots” Sanders says — there has been a paucity of long-term cohort studies focused on the gastrointestinal aspects of Parkinson’s disease The result is a lack of knowledge about how the gut microbiome might shift as the disease progresses Sanders co-leads the Coordinating and Data Management Center for the Gut–Brain Communication in Parkinson’s Disease Consortium an effort launched last year by the US National Institutes of Health (NIH) to gather detailed information on gut symptoms and microbiome alterations in people with Parkinson’s The team is now developing protocols for recruitment of participants and is “cautiously optimistic” about having its funding renewed for a second year despite the disruptions to NIH research that have occurred during US President Donald Trump’s administration Payami is also continuing to track gut microbiome changes in individuals who have been part of previous studies in her lab — a total of 180 people with Parkinson’s and 130 healthy controls with between 4 and 8 years of follow-up so far Payami expects to complete analysis of microbial DNA sequences from these samples this summer Payami is optimistic about the potential of gut-based therapies for Parkinson’s Even if the pathology doesn’t begin in the gut and offering relief for these symptoms is worthwhile in itself If therapies targeting the gut microbiota could slow disease progression too doi: https://doi.org/10.1038/d41586-025-01253-2 Payami, H., Sampson, T. R., Murchison, C. F. & Wallen, Z. D. Preprint at medRxiv https://doi.org/10.1101/2024.04.03.24305273 (2024) Download references Fungus from the human gut slows liver disease in mice Diet outperforms microbial transplant to drive microbiome recovery in mice Baffling chronic pain eases after doses of gut microbes Reframe perspectives on Alzheimer’s disease better: the rise of blood tests for Alzheimer’s The unusual genetic inheritance that could change Alzheimer’s treatment UNIL is a leading international teaching and research institution with over 5,000 employees and 17,000 students split between its Dorigny campus Department of Energy and Environmental Materials and advance cancer research in a leading translational institute Olivia Newton-John Cancer Research Institute We are seeking a tenure-track associate professor to promote interdisciplinary research in nanoprobe life sciences or related interdisciplinary field • Studying the development and metabolism of lymph nodes through melanoma metastasis Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V Sign up for the Nature Briefing newsletter — what matters in science Syngenta has been besieged by lawsuits from people claiming its product caused the neurological condition A court filing on Monday confirmed that a letter of agreement between the parties had been signed. In a court hearing on Tuesday, one of the lead plaintiff lawyers, Khaldoun Baghdadi, said the terms of the settlement should be completed within 30 days. Read moreThe move to settle comes amid mounting calls from state and federal lawmakers to ban paraquat, and as growing numbers of Parkinson’s patients blame the company for not warning them of paraquat risks. Numerous scientific studies have linked Parkinson’s to exposure to paraquat, a weedkiller commonly used in agriculture, though Syngenta has said the weight of scientific evidence shows its pesticide does not cause the disease. The agreement would not resolve all of the cases filed in the United States against Syngenta, but could resolve the majority of them. As of mid-April, there were more than 5,800 active lawsuits pending in what is known as multi-district litigation (MDL) being overseen by a federal court in Illinois. There were more than 450 other cases filed in California, and many more scattered in state courts around the country. The agreement notice applies to people whose lawsuits are part of the MDL, and could provide settlements for plaintiffs in the cases outside the MDL as well, said Baghdadi. “Syngenta has settled certain claims in the federal Multi-District Litigation (MDL) and California court in the United States related to paraquat,” the company said. “Syngenta believes there is no merit to the claims, but litigation can be distracting and costly. Entering into the agreement in no way implies that paraquat causes Parkinson’s disease or that Syngenta has done anything wrong. We stand by the safety of paraquat. “Despite decades of investigation and more than 1,200 epidemiological and laboratory studies of paraquat, no scientist or doctor has ever concluded in a peer-reviewed scientific analysis that paraquat causes Parkinson’s disease.” Syngenta’s effort to settle the litigation before any high-profile trials comes after Monsanto’s owner, Bayer, was rocked by similar litigation alleging its Roundup weedkiller causes cancer. After the company lost the first Roundup trial, its stock price plummeted, and Bayer has spent years and billions of dollars fighting to end the ongoing litigation. Lawyers for paraquat plaintiffs in cases outside the MDL expressed frustration with the situation, saying they were not included in the settlement discussions, and were not being given details about the settlement. Read moreThey fear their cases may be delayed or otherwise negatively affected by a settlement that benefits some plaintiffs but may not actually provide value to the majority of them “These plaintiffs are dying every day,” Majed Nachawati a lawyer whose clients are outside the MDL told a judge in a California court hearing on Tuesday on the matter He said the news of the settlement was a “shock” because he was not apprised of the settlement negotiations by the other plaintiffs’ lawyers Paraquat has become one of the most widely used weedkilling chemicals in the world This story is co-published with the New Lede a journalism project of the Environmental Working Group Researchers have suspected for some time that the link between our gut and brain plays a role in the development of Parkinson's disease "Supplementation of riboflavin and/or biotin is likely to be beneficial in a subset of Parkinson's disease patients, in which gut dysbiosis plays pivotal roles," Nagoya University medical researcher Hiroshi Nishiwaki and colleagues wrote in their paper published in May 2024 The neurodegenerative disease impacts almost 10 million people globally, who at best can hope for therapies that slow and alleviate symptoms Symptoms typically begin with constipation and sleep problems up to 20 years before progressing into dementia and the debilitating loss of muscle control Previous research found people with Parkinson's disease also experience changes in their microbiome long before other signs appear Analyzing fecal samples from 94 patients with Parkinson's disease and 73 relatively healthy controls in Japan Nishiwaki and team compared their results with data from China While different groups of bacteria were involved in the different countries examined they all influenced pathways that synthesize B vitamins in the body The researchers found the changes in gut bacteria communities were associated with a decrease in riboflavin and biotin in people with Parkinson's disease Nishiwaki and colleagues then showed the lack of B vitamins was linked to a decrease in short-chain fatty acids (SCFAs) and polyamines: molecules that help create a healthy mucus layer in the intestines "Deficiencies in polyamines and SCFAs could lead to thinning of the intestinal mucus layer, increasing intestinal permeability, both of which have been observed in Parkinson's disease," Nishiwaki explains They suspect the weakened protective layer exposes the intestinal nervous system to more of the toxins we now encounter more regularly. These include cleaning chemicals, pesticides Such toxins lead to the overproduction of α-synuclein fibrils – molecules known to amass in dopamine-producing cells in the substantia nigra part of our brains eventually leading to the more debilitating motor and dementia symptoms of Parkinson's A 2003 study found high doses of riboflavin can assist in recovering some motor functions in patients who also eliminated red meat from their diets So it's possible that high doses of vitamin B may prevent some of the damage This all suggests ensuring patients have healthy gut microbiomes may also prove protective, as would reducing the toxic pollutants in our environment with such a complicated chain of events involved in Parkinson's disease not all patients likely experience the same causes so each individual would need to be assessed "We could perform gut microbiota analysis on patients or conduct fecal metabolite analysis," explains Nishiwak we could identify individuals with specific deficiencies and administer oral riboflavin and biotin supplements to those with decreased levels potentially creating an effective treatment." This research was published in npj Parkinson's Disease An earlier version of this article was published in June 2024 Sign-up to the latest news from Australian Women’s Weekly Disclaimer: By joining, you agree to our Privacy Policy & Terms of Use Amanda Keller has once again candidly opened up about her husband Harley Oliver’s Parkinson’s disease The radio host is also currently hosting a new ABC series which sees everyday pianists sit down and play a tune or two on a piano in various busy locations throughout the country She previously appeared on The Assembly – a documentary series that follows a team of autistic journalism students one student asked Amanda if she loved her husband Amanda became visibly emotional and told the student that her question was “beautiful” before answering: because my husband is going through some stuff at the moment “My husband has Parkinson’s disease We’re learning to find ourselves in the midst of changing circumstances and part of me thinks – it’s easy for me to say he’s the one going through it – but part of me thinks it’s a real privilege to be with someone long enough that you go through these changes with them even though we’ve got some stuff going on.” asked why Amanda and Harley announced his diagnosis to the public Amnda replied that they’d done so for “a couple of reasons” “One is that I work on breakfast radio and a big part of that is sharing your life – and even though it wasn’t my story to tell “Another reason I wanted to was that I wanted to open the window into why people look at us strangely when we’re out Harley felt that people might think he was drunk or they’d look at me and they’d look at him and think what’s going on?’ I wanted to free us up by saying ‘Here’s what’s going on.’ I think that’s why I did it.” “I do appreciate that by speaking publicly about it and some days that’s hard – but I’m glad I did.” This isn’t the first time Amanda has bravely shared details about her husband’s condition during an appearance on the June 22 episode of Stellar’s podcast Something To Talk About Amanda was asked how Harley is doing in light of his condition He just gets on with it,” she candidly replied “And I’ve gone through a phase of being angry because I’d say things to him like “I knew what it was; he’d been diagnosed And I feel now I’m very much on the path of acceptance – or that radical acceptance that’s a phrase that I’m trying to live and other days I do feel it Amanda then went on to share the lovely analogy her kinesiologist taught her Saying that it ultimately helped her process Harley’s Parkinson’s as well as her son leaving home ‘You’re in a boat beside Harley and you take his agency away by trying to.’ We’d had a similar conversation when my son left home – I still want to cry about that ‘Can I be in the back of the boat?’ She said It’s his shining light that’s navigating it.’ “It’s similar with Harley in that I know I’m trying to make everything right for everybody and a) you can’t because you’ll exhaust yourself but b) that’s not what’s right for everybody.” Amanda took to Instagram on June 3 and shared a sweet throwback picture of herself and Harley in honour of their 34th wedding anniversary a photo pops up in your memories just when you need to see it Harley and I celebrated our 34th wedding anniversary last week This pic must have been taken just a few years later,” Amanda wrote “Harley’s Parkinson’s disease has sent a variety of challenges that he accepts with stoicism and grace (more so than I do) But the essence of ‘him’ and ‘us’ remains It’s the stuff we all face as we age and grow and morph during the May 20 episode of Jonesy & Amanda she broke down in tears live on-air while discussing how Harley’s Parkinson’s stopped him from attending their son’s 21st birthday party… Or so she thought “Leaving the house to go to Jack’s party it’s not right that Harley can’t come I really felt lonely thinking it’s our son’s 21st but how hard it is for Harley and how much he would have loved to have been there,” Amanda said The speeches are about to start and my friend Kate said to me ‘There’s Harley.’ And I looked over He and our friend Pam and our driver friend Cole had conspired to get Harley there for the speeches And it was so moving,” she continued “And a lot of people were shocked because they hadn’t seen Harley for a while Amanda first publicly shared her husband’s Parkinson’s disease diagnosis in October 2023 she noted that he actually received the diagnosis six years prior During an episode of the Double A Chattery podcast an emotional Amanda revealed she avoided sharing the sad news until it felt like the right time “Harley has Parkinson’s disease,” the Living Room host said “This has impacted him and us and the way we live our lives in many different ways.” Amanda first realised something was wrong when she noticed her partner dragging his foot around the house While Harley put it down to an old cricket injury Amanda knew something more sinister was at play Amanda confessed she and Harley were “completely numb” I was cross with him,” the presenter confessed ‘Why isn’t he fighting it?’ But I’ve come to see you can’t control this I’ve become kinder and sadder.” Amanda then brought in her husband to chat about his disease “It’s been a journey between us,” Harley said to his wife “It’s a constant thing; it’s every day you can’t tell how long it’s going to last before it really starts to bite.” Harley went on to say he’s “lucky” that the disease is “so slow”. Because of that, he can develop tactics to fight it adding that there are other people a lot worse off than him The emotional interview ended with the couple trading words of support and love “You can’t choose your dismount but I always choose you,” Amanda said to her husband Amanda first met Harley while she was a researcher for the children’s show Simon Townsend’s Wonder World! Her future husband was a producer on the show The pair married in 1989 and now share two sons “Amanda is a very full-on mum,” Harley told The Weekly in 2022 “But she’s a very natural mum as well Catie Powers is a digital journalist and a lover of all things fashion She also manages the print-to-digital relationship for The Australian Women's Weekly Subscribe and be in with the chance of winning $25,000 cash or prize pack exclusive content via our monthly subscriber newsletter ShareSaveCommentInnovation HealthcareHow The Shortage Of Parkinson’s Disease Specialists Is ChangingByBruce Y. Lee Forbes contributors publish independent expert analyses and insights Safra Fellowship in Movement Disorders has trained 40 new .. Safra Foundation partnering together to address Parkinson's Disease research and care. Fox cutting the ribbon to launch the partnership in 2014 (Photo: Courtesy of Kristina Magana/Michael J chief executive officer and co-founder of MJFF recalled what happened when the Safra Foundation first came to ask for opinion “They wanted to support great PD care and research centers coming through the lens of science support We said what if we shaped it as a way to train future researchers and care providers.” Brooks continued by saying “We don’t have many movement disorder specialists That was a little over a decade ago. Such conversations eventually led to the 2014 launch of the Edmond J. Safra Fellowship in Movement Disorders which has since trained 40 new clinician-researchers These graduates of the training fellowship have in turn reached 31,200 different patients with PD so far by their estimates this partnership will keep the train going The two foundations have just announced that this fellowship will stretch into 2031 which would mean graduating another 101 new movement disorder specialists That in turn could reach 78,780 more patients with PD which could make many very tough situations significantly less tough you may know someone personally who is dealing with PD That’s because PD is at this moment the second most common and fastest-growing neurological disease in the world close to 90,000 PD cases are newly diagnosed each year There’s already an estimated 6 million people globally living with PD Pictured here are attendees of the 2018 Edmond J you may not know movement disorder specialists which is another name for the neurologists with extra training and experience to address PD That’s because the United States has only around 660 movement disorder specialists at this moment that comes out to only about one such specialist for every 1,000 Medicare beneficiaries with PD That ratio probably isn’t equally spaced around the country either PD is considered a movement disorder because it can affect how a person is able to move difficulty initiating movements and postural instability which is when a person has difficulty maintaining balance and is more likely to fall There are also non-motor challenges like mood changes as well as difficulty sleeping and thinking But things can be done to reduce the impact of symptoms and potentially slow the progression Not everyone will know the latest and greatest on such things who is the principal medical advisor for the Michael J Fox Foundation and a movement disorder specialist herself explained that while primary care doctors and neurologist who are not movement disorder specialists may be able to offer reasonable care it makes a difference if you have an expert who has seen many different variations of PD and has PD as a main focus “You need someone involved in your treatment regimen and involving your care team with connections to occupational therapy and physical therapy.” She added that it helps to have someone up on the latest advances knowledge and skill set to implement such treatments in the right people.” Specialists can also help diagnose the condition earlier it can take a while for someone with PD to get an official diagnosis “Patients find their way to doctors,” said Brooks “They often are not aware that specialty care exists.” patients can end up bouncing around the healthcare system among the wrong kinds of healthcare professionals like a pinball they may even be told that their PD symptoms are nothing due to something else like anxiety or a musculoskeletal injury or even worse all in their head that’s what you want to hear when you’ve got a real condition that people are just not catching That doesn’t mean that other healthcare professionals are not trying or able to properly PD It’s just that things often can get tricky “PD remains a clinical diagnosis,” Dolhun emphasized That means that you can only diagnose it via putting together different aspects of the patient’s history and physical exam where there’s a clear test to establish the diagnosis the symptoms are not obvious like diarrhea You won’t hear too many people say something like “It’s not clear that you have diarrhea.” The same can’t always be said about PD symptoms “You want an expert who sees PD regularly who can recognize and diagnose it accurately.” Patients can be especially likely to get misdiagnosed when they don’t match what’s believed to be the “typical PD profile.” Dolhun explained “There’s the misperception that it is an old white man’s disease.” She added Delayed diagnoses can not only waste time and medical resources but also keep the patient in an uncomfortable limbo Dolhum related that once patients learn what’s really going on they frequently end up feeling “I don’t want this answer but it is nice to have an answer.” Diagnosing someone as soon as possible can then get them into the right treatment programs sooner What’s been making a difference in making such differences is the Edmond J Safra Foundation partnership has been providing selected academic institutions the funding to offer additional training to neurologists wanting to focus on movement disorders Each of the institutions then find the right fellow to hire and train “The institutions were selected based on their ability to mentor and support the candidates,” said Brooks “Diversity and inclusion is important.” She added We’ve essentially doubled the program over the course of 10 years This is building a network and the next generation of specialists expanding educational and research collaboration opportunities.” The funding was crucial because PD care and research aren’t exactly rolling in the dough People don’t say that they will be entering the movement disorder specialty for the big bucks Dolhum described care of movement disorder as “a talking specialty” and that “talking doesn’t get the reimbursement,” compared to procedures Insurance companies may view talk as cheap But what movement disorder specialists can do for patients is far from that “Getting to a movement specialist early is a sign that you are empowered,” Dolhum emphasized Both Dolhum and Brooks pointed out how proper specialty care can improve patient outcomes in many different ways Some of these outcomes may be easy to measure whereas others may be complex This website may not work correctly in Internet Explorer. We recommend switching to a more secure modern web browser such as Microsoft Edge which is already installed on your computer View this website in Edge. New international research led by Western Australian neurologists and scientists highlights the potential for precise and personalised treatment of Parkinson’s disease As Parkinson’s is a complicated disorder driven by multiple processes comprehensive therapeutic strategies are likely to be required in parallel with a personalised approach ‘A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease’ until recently with the Perron Institute and now Associate Research Scientist at the Department of Neurology and Adams Center for Parkinson’s Disease Research “The connection between alpha-synuclein (α-synuclein) a neuronal protein encoded by the SNCA gene representing a milestone in Parkinson’s research,” Dr Li said researchers have been working to understand the function and underlying mechanisms of how α-synuclein causes Parkinson’s and to develop effective disease-modifying therapeutic strategies “Reducing α-synuclein levels and removing its aggregates has been the current focus of new experimental therapies for Parkinson’s disease evidence has been emerging that the process of α-synuclein aggregation may in fact lead to a deficiency of the soluble functional form of the protein in neurons and that this may need to be replenished to sustain neuronal function we propose a personalised and comprehensive approach for treating different Parkinson’s subgroups based on whether α-synuclein is likely to contribute to disease pathogenesis through an excess (“gain-of-function”) or a depletion of the protein (“loss-of-function”) or through a combination of both mechanisms “Our perception is that the ideal disease-modifying strategy should comprise a combination of personalised approaches We believe a biological or biochemical definition of α-synuclein could be the key to the discovery of novel therapies targeting underlying disease pathogenesis “Getting the right treatment for Parkinson’s is challenging but we are optimistic that continued investigation of therapeutic approaches targeting α-synuclein will lead to improved quality of life for people with Parkinson’s,” Dr Li said Perron Institute senior advisor and Clinic co-founder Professor Frank Mastaglia is senior author of the research paper Other authors are Perron Institute Consultant Neurologist Dr Wayne (Wai Yan) Yau Professor Steve Wilton (Perron Institute and Murdoch University) Department of Neurology and Institute of Neurology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Stay up to date with our latest news and announcements The Perron Institute wishes to acknowledge the traditional custodians of the land on which our services are delivered – the people of the Noongar Nation We acknowledge and pay respect to the Noongar people’s ongoing culture as well as their rich contribution to life in this region Metrics details There is limited data about experiences of people with Parkinson’s (PwP) in Australia surveyed 385 participants nationally (335 fully completed the questionnaire) Participants living in capital and regional city centers reported satisfaction with clinical care during diagnostic consultation at approximately 40% with satisfaction less in rural areas (26%) 68% of participants reported inadequate involvement in discussions about treatment and care planning and 77% were dissatisfied with the support following diagnosis Respondents reported low referral rates to allied health services such as physiotherapy (22%) and mental health services (17%) Feedback indicated support could improved by increased access to Parkinson’s disease Clinical Nurse Specialists and to educational resources and support Findings highlight the need to establish Australian guidelines for Parkinson’s clinical management greater resourcing for clinicians including development of educational programs and creation of Australian-centric educational resources to improve quality of care for PwP require long-term multi-disciplinary care to manage their complex spectrum of symptoms Findings from these studies cannot be readily translated to PwP experiences in the Australian setting due to major differences in healthcare system models as PwP can be triaged through both public or private options Access to healthcare providers in Australia is also heavily influenced by geographical factors and therefore did not inform patient experiences nationwide there have been no Australia-wide studies focusing on the patient perspective from initial symptom presentation to diagnosis provide some important insights into the patient experience including PwP in Australia methods used such as small patient cohorts and single state studies rather than nationwide we undertook this study which aimed to examine unbiased experiences of PwP in their journey to diagnosis clinical care and community-based support from PwP across Australia we aimed to generate evidenced-based data by collecting suggestions reported by PwP on how they believe patient experience could be improved and what additional supports are needed within the community Findings from this study can be used for quality improvement in the diagnostic process clinical care and communications with the PwP Data generated in this study will identify gaps in clinical and community care which can influence long-term health outcomes and QoL indicators in PwP completed the questionnaire and there were a similar proportion of male (n = 157 The mean age of participants was 66 years old (SD = 10) most respondents lived in Australia’s three most populated states Participants were also stratified into three groups based on self-reported geographical location Over half the participant cohort in this study resided in capital cities across Australia (58%) 67% (ABS) of Australians lived in capital cities) This figure shows (a) at what age (years) participants received a clinical diagnosis of PD (N = 329) b The time taken to be diagnosed with PD following onset of first symptoms (N = 329) The median time from first symptom to diagnosis was 2 years [IQR = 1,4] c The time taken to receive a diagnosis of PD based on gender “My experience was more about the lack of knowledge by GP’s and Specialists regarding the symptoms demonstrated. It took a full year of pain and all sorts of treatment by numerous Doctors before I was diagnosed.” – Participant 134 “My GP misdiagnosed me for 3 years. In the end I demanded a referral to a neurologist and flew interstate from NT to WA.” – Participant 182 I feel anyone that struggled using the internet would really struggle to have an understanding of the disease. I have spent many hours researching. I think a package on diagnosis would be a start.” – Participant 56 “I feel that the treating Neurologist could be more supportive and forthcoming with information that is of use.” – Participant 72 “Many of us leave the ‘diagnosis’ consultation unprepared for the news, often alone and without even a brochure explaining what PD is and where to access information and support services.” – Participant 151 “The availability of a multi discipline center for advice and information especially when first diagnosed. Advice not just on medication but also on exercise, diet, meditation/stress relief, supplements would be very beneficial.” – Participant 34 “Information about allied health support, exercise groups, speech pathology, dieticians.” “Doctors, neurologists but more realistically GPs, to have a list of services available in an area, such as exercise classes, allied health professionals (speech pathologists etc) to suggest / direct patients.” – Participant 118 “I did most of my research online. I suppose it would be nice if all that stuff could be held in one place / app to make the process easier and quicker.” – Participant 26 “An app with a variety of supportive information will be practical and beneficial.” – Participant 86 were asked to select from six categories preferences for sourcing additional support in the community following diagnosis Options ranged from the use of educational and clinical apps newsletters from academic research institutions and attending in-person PD community support groups of participant preferences for each category provided free text suggestions or recommendations for how PwP could be better supported following diagnosis Free text responses were categorized into 18 areas of additional support as shown above of participant suggestions/recommendations for each category accessibility due to financial constraints particularly the out-of-pocket costs associated with genetic testing especially for more comprehensive options such as whole genome or whole exome sequencing along with the need for genetic counseling and the perceived limited clinical utility continue to present significant barriers to the widespread implementation of these tests in clinical practice findings from this same study showed PwP felt there was a lack of time to discuss treatment options at scheduled appointments and in some cases interacting with different health care professionals over multiple clinical visits reduced opportunities for discussion we didn’t see discussions about treatment options and symptom management as being a barrier to shared decision-making given participants reported mainly positive feedback to being informed about medications and symptom management (72%) from free text responses many participants in our study reported they experienced a lack of time at scheduled appointments for discussion with their treating clinicians and at the time of receiving the diagnosis the initial shock they experienced prevented them from engaging in discussion about treatment options and care plans participants communicated that they would have liked an opportunity to ask further questions in a follow up appointment soon after receiving their diagnosis with their treating clinician or a PD nurse specialist when they were in a better state of mind findings from our study have identified a gap in the diagnostic process where there is a need for improved resources and training in clinician-patient communication and provision of centralized and consistent information to best meet the individual’s needs relevant to disease stage for promotion of best clinical practice to improve patient experience and perceptions of quality of care understanding individual needs and priorities is important to determine the provision of healthcare support and improved access to specialist health services would also have a positive impactful on QoL leverages support for the development of Australian PD clinical apps which in the future may be implemented into routine clinical practice by neurologists and movement disorder specialists It should be noted there are a few PD apps developed in Australia including The Walking Tall app and The Speak Up for Parkinson’s app these are used for the management of specific symptoms associated with PD such as walking and speech impairments These apps do not provide self-management of disease in terms of symptom tracking tracking QoL indicators or facilitating communication with clinical care teams between scheduled appointments these are generally restricted for use by participants enrolled in clinical trials and the information provided are generally region-specific e.g Development of universally accessible apps with enhanced capabilities for symptom tracking could provide additional support for those with PwP whilst also providing relevant standardized information on global PD with respect to motor and non-motor symptoms for example the latest research and advice on emerging therapies report limited information and referral to community support services and organizations when receiving a diagnosis this has resulted in the increased use of the internet and other digital resources as a means of accessing information over 60% participants in our study indicated they would like access to a general PD app and other electronic or digital resources which provides access and linkage to Australian generated resources and community support organizations Currently most Australian PD resources are limited to information provided on PD organizational websites These websites are an important source of broad and general information about disease although linkage or referral to local and state PD clinical specialists or allied and mental health service providers can be limited or varied Clinically aligned resources provided on Australian PD websites are also linked to international organizations such as The Michael J Fox Foundation or The Davis Phinney Foundation which are a good source of general information but do not necessarily provide information that applies to PwP in Australia There are limited resources generated for PwP in the Australian context This was represented in qualitative feedback from both PwP and carers who stated they felt overwhelmed trying to navigate the varied and often unverified information available on the internet and it promoted anxiety for many as they were unsure if the information was accurate and relevant to their stage of disease the uneven quality of online health information itself can have a major impact on PwP and can further influence physician-patient relationships Despite several limitations associated with the present study strengths of this study are that this is the largest representative survey of PwP to date across all states and territories of Australia examining the diagnostic process and patient experience the findings presented here provide new information relevant to Australia and suggest opportunities for improved support addressing the needs of PwP findings reported in this Australian study reveal gaps in the perceived quality of care for PwP by clinicians and medical experts during the diagnostic consultation and highlight the need for greater funding to better enable and support healthcare providers Participant responses suggest that PD healthcare in Australia is under-resourced and there is a lack of provision and referral by treating physicians to allied and mental health service providers for additional support in the community following diagnosis and improved access to GP Management Plans through the Medicare scheme could help address this gap Management Care Plans provide subsidized access to much needed allied health services based on individual healthcare needs and personal QoL priorities outcomes from this study show the current approach to care for PwP in Australia is neither patient-centered nor holistic Current findings can be used to leverage increased funding by healthcare legislators for the generation of Australian guidelines for the management of PD establishment of specialized clinician PD training programs and development of Australian-relevant resources to improve the quality of patient-centered care in Australia Participants were eligible if they resided in Australia or were someone providing carer support for a PwP We used a maximum variation strategy and recruited across all stages of disease and subgroups of PD The questionnaire was distributed through various advertising methods to capture a range of people across Australia (refer to “Data collection”) Data was collected over a 10-month period (February to December The questionnaire was completed by respondents through various channels including (1) social media (Facebook/Instagram) (2) PD organization and community support group web pages and (iii) the Walter and Eliza Hall Institute webpage flyers with a QR code for access to the questionnaire were distributed to rural and regional PD organizations PD community support groups and displayed within movement disorder clinical consulting rooms nationwide The questionnaire took approximately 20 min to complete Descriptive statistics were used to summarize the demographic and clinical characteristics as well as the participant experiences Associations between first symptoms (three categories; motor only and years to diagnosis were tested using Kruskal–Wallis rank sum tests Differences in participant responses to experience of clinical care were examined by first dichotomizing responses to agree (strongly agree Associations with state or territory (8 categories) were tested using Fisher’s exact test with asymptotic Chi-squared probabilities utilized where all cell had expected counts between ≥1 and >80% of cells had expected counts of at least 5 Associations with geographical region (three categories; capital city were tested using Chi-squared tests of independence All analyses were performed using R software version 4.3.1 This study was approved by the Walter and Eliza Hall Institute of Medical Research Human Research Ethics Committee (HREC reference # 22/30) Implied consent was obtained from participants if they chose to start completing the questionnaire after reviewing an information page which outlined the purpose of the research and requirements for participation in the study Participants and carers who started answering the questionnaire and submitted responses were deemed to have sufficient capacity for implied consent in this non-interventional This study was conducted in accordance with the principles embodied within the Declaration of Helsinki The data set analyzed in the current study is available from the corresponding author on reasonable request Challenges in the diagnosis of Parkinson’s disease Recent advances in biomarkers for Parkinson’s disease Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis Evaluation of nonmotor symptoms in diagnosis of Parkinsonism and tremor Identifying subtle motor deficits before Parkinson’s disease is diagnosed: what to look for Disease modification in Parkinson’s disease: current approaches The diagnostic pathway of Parkinson’s disease: a cross-sectional survey study of factors influencing patient dissatisfaction Global Parkinson’s Disease Survey Steering C Factors impacting on quality of life in Parkinson’s disease: results from an international survey Capturing patients’ experiences to change Parkinson’s disease care delivery: a multicenter study Patient experiences of receiving a diagnosis of Parkinson’s disease survey of patients with Parkinson’s disease: satisfaction with medical care and support groups Treatment satisfaction and its influencing factors in Parkinson’s disease: a web-based survey of patients and physicians in clinical practice in Japan What matters to people with Parkinson’s disease living in Australia? A cross-sectional study of clinical management and provision of health services and their utilisation by patients with Parkinson’s disease in urban and regional Victoria Health care experiences of people with Parkinson’s disease in Australia Australian Parkinson’s Genetics Study (APGS): pilot (n=1532) Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study Personalized medicine in Parkinson’s disease: time to be precise The initial diagnosis and management of Parkinson’s disease Integrated and patient-centred management of Parkinson’s disease: a network model for reshaping chronic neurological care An evaluation of the patient education programme for Parkinson’s disease in clinical practice Parkinson’s disease: summary of updated NICE guidance Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease The patient’s perspective on shared decision-making in advanced Parkinson’s disease: a cross-sectional survey study Moving towards patient-centered healthcare for patients with Parkinson’s disease Personalised care planning for adults with chronic or long-term health conditions Allied health care in Parkinson’s disease: referral Move for change part II: a European survey evaluating the impact of the EPDA Charter for people with Parkinson’s disease Experiences of health service access and use for people living with Parkinson’s disease in Ireland: a national survey Psychiatric manifestation in patients with Parkinson’s disease A systematic review of prevalence studies of depression in Parkinson’s disease Prevalence of anxiety in Parkinson’s disease: a systematic review and meta-analysis Improving Parkinson’s disease care through systematic screening for depression A narrative review of specialist Parkinson’s nurses: evolution The role of Parkinson nurses for personalizing care in Parkinson’s disease: a systematic review and meta-analysis Using an economic evaluation approach to support specialist nursing services for people with Parkinson’s in a regional community Parkinson’s disease movement disorder nurse specialist demographic survey 2021 2022 annual demographic survey of Parkinson’s disease and movement disorder nurse specialists Parkinson’s disease and the COVID-19 pandemic Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson’s disease Exploring Parkinson’s disease prevalence in regional rural and remote Australia: a systematic scoping review Socioeconomic status and racial or ethnic differences in participation: web-based survey Self-reported data in environmental health studies: mail vs Patient satisfaction with healthcare services and the techniques used for its assessment: a systematic literature review and a bibliometric analysis Socio-economic differences in participation of households in a Belgian national health survey The REDCap consortium: building an international community of software platform partners Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support Download references This study was funded through The Walter and Eliza Hall Institute of Medical Research We would like to thank the Parkinson’s Disease Consumer Reference Group for their comments on the manuscript We would like to thank the Parkinson’s community of Australia for participating in this study We would like to thank Parkinson’s Disease support organizations throughout Australia and Shake It Up Foundation Australia for supporting our research activities by sharing the survey link with their communities Victor McConvey and Jane Alty for comments and feedback is supported by a Fellowship from the Bodhi Education Fund This work was supported by operational infrastructure grants through the Australian Government Independent Research Institute Infrastructure Support Scheme (9000587) and the Victorian State Government Operational Infrastructure Support was supported by philanthropic funding by Leon and Annette Davis These authors contributed equally: Iain McLean Walter and Eliza Hall Institute of Medical Research contributed to research design and conceptualization of the study and wrote the original draft of the manuscript contributed to the analysis and interpretation of data contributed to data analysis and writing of the manuscript contributed to the conceptualization and design of the study the acquisition of data and writing the manuscript contributed to the design of the survey and acquisition of data contributed to the clinical interpretation and revision of manuscript for intellectual content All authors contributed to the preparation of the manuscript The authors declare no competing interests Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41531-025-00968-3 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Researchers from Ruhr University Bochum’s PRODI Center for Protein Diagnostics developed the iRS test that identifies misfolded alpha-synuclein proteins in spinal fluid The technology achieved 95% accuracy in distinguishing between individuals with and without Parkinson’s disease when tested across two independent studies involving 134 participants “Parkinson’s disease is characterized by the loss of dopaminergic nerve cells in the brain which usually leads to increasing motor impairments as the symptoms progress,” explained Professor Klaus Gerwert the study’s lead researcher and PRODI’s founding director The challenge with Parkinson’s diagnosis lies in timing. By the time characteristic symptoms like tremors and walking difficulties appear more than half of the brain’s dopamine-producing cells have already died The progressive nature of the condition means brain damage is often irreversible by the clinical diagnosis stage The iRS testing approach measures the structural changes in alpha-synuclein proteins which transform from normal alpha-helical shapes to beta-sheet formations in Parkinson’s patients The misfolded proteins eventually form larger complexes called oligomers ultimately creating the familiar Lewy bodies found in Parkinson’s patients’ brains the iRS technology provides more than a simple positive or negative result Researchers noted it measures a continuum of protein misfolding potentially allowing doctors to track disease progression and treatment effectiveness over time The research team had previously applied this technology to Alzheimer’s disease detection where it successfully predicted dementia risk up to 17 years before clinical diagnosis The platform’s adaptation to Parkinson’s represents an important advance in neurological disease detection The study’s authors emphasize that early detection could enable interventions before significant neurological damage occurs While current treatments focus on managing symptoms through dopamine supplements earlier diagnosis might eventually support preventive therapies targeting protein misfolding before substantial cell loss happens document.addEventListener( 'DOMContentLoaded' function () {const newsletterAsset = new HMIRegistration({ publicationId: 8 bootstrap: document.getElementById('newsletter-asset') formType : "user-initiated",pubType: "business"});newsletterAsset.mount();}); Please login or register first to view this content Only subscribers can update their account from this page CNN and the BBC World Service which is copyright and cannot be reproduced AEST = Australian Eastern Standard Time which is 10 hours ahead of GMT (Greenwich Mean Time) If you would like to give to a specific research program or support the work of a particular researcher WEHI researchers have made a huge leap forward in the fight against Parkinson’s disease solving a decades-long mystery that paves the way for development of new drugs to treat the condition PINK1 is a protein directly linked to Parkinson’s disease – the fastest growing neurodegenerative condition in the world no one had seen what human PINK1 looks like how PINK1 attaches to the surface of damaged mitochondria researchers at the WEHI Parkinson’s Disease Research Centre have determined the first ever structure of human PINK1 bound to mitochondria The work could help find new treatments for the condition that currently has no cure or drug to stop its progression there are close to 40 symptoms including cognitive impairment body temperature regulation and vision problems over 200,000 people live with Parkinson’s and between 10% and 20% have Young Onset Parkinson’s Disease – meaning they are diagnosed under the age of fifty The impact of Parkinson’s on the Australian economy and healthcare systems is estimated to be over $10 billion each year Mitochondria produce energy at a cellular level in all living things and cells that require a lot of energy can contain hundreds or thousands of mitochondria which supports cell survival by detecting damaged mitochondria and tagging them for removal PINK1 gathers on mitochondrial membranes and signals through a small protein called ubiquitin that the broken mitochondria need to be removed The PINK1 ubiquitin signal is unique to damaged mitochondria Although PINK1 has been linked to Parkinson’s and in particular Young Onset Parkinson’s Disease researchers had been unable to visualise it and did not understand how it attaches to mitochondria and is switched on Corresponding author on the study and head of WEHI’s Ubiquitin Signalling Division, Professor David Komander said years of work by his team have unlocked the mystery of what human PINK1 looks like and how it assembles on mitochondria to be switched on “This is a significant milestone for research into Parkinson’s It is incredible to finally see PINK1 and understand how it binds to mitochondria,” said Prof Komander who is a laboratory head in the WEHI Parkinson’s Disease Research Centre “Our structure reveals many new ways to change PINK1 which will be life-changing for people with Parkinson’s.” WEHI senior researcher Dr Sylvie Callegari with the first two steps not been seen before which then links to a protein called Parkin so that the damaged mitochondria can be recycled “This is the first time we’ve seen human PINK1 docked to the surface of damaged mitochondria and it has uncovered a remarkable array of proteins that act as the docking site how mutations present in people with Parkinson’s disease affect human PINK1,” said Dr Callegari The idea of using PINK1 as a target for potential drug therapies has long been touted but not yet achieved because the structure of PINK1 and how it attaches to damaged mitochondria were unknown The research team hope to use the knowledge to find a drug to slow or stop Parkinson’s in people with a PINK1 mutation One of the hallmarks of Parkinson’s is the death of brain cells Around 50 million cells die and are replaced in the human body every minute the rate at which they are replaced is extremely low they stop making energy and release toxins into the cell the damaged cells are disposed of in a process called mitophagy In a person with Parkinson’s and a PINK1 mutation the mitophagy process no longer functions correctly and toxins accumulate in the cell Brain cells need a lot of energy and are especially sensitive to this damage Dr Sylvie Callegari and Dr Alisa Glukhova in front of an image of PINK1 Your support will help WEHI’s researchers make discoveries and find treatments to ensure healthier Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" We acknowledge the Wurundjeri people of the Kulin Nation as the traditional owners of the land where our campuses are located and recognise their continuing connection to Country and community WEHI is committed to fostering an inclusive workplace where people with diverse identities can flourish in a safe and supportive environment By using this website, you agree to our use of cookies in accordance with our Privacy Policy and Terms of use Utah native Tori Parkinson won the 27th Flying Pig Marathon on Sunday in 2 hours "My training wasn't exactly what I wanted it to be so I was really happy to feel strong when the later miles kicked in," Parkinson said opening up a sizable gap by the time she came off the Clay-Wade Bailey Bridge at about mile 4 she had opened up an eight-minute gap on Emma Bell and Daniella Townsend she mistook some of the female half-marathon leaders as her fellow competitors It wasn't until the split in Walnut Hills that she realized she was all alone Despite running by herself for the majority of the race she clocked an even split of 1:19:41 for the first half and 1:20:25 for the second half Men's winner: 'It's very exciting.' St. Henry High School alum Sean Ryan wins Flying Pig Marathon Half-marathon winners: Jonathan Harley, Maddy Trevisan set course records in Flying Pig Paycor Half Marathon wins "I would channel some of the runs I've done at home and pictured what those felt like Playing the mental games through it really helped me the most," Parkinson said Parkinson raved about the energy on the course saying it "might be my favorite marathon I've ever done." Her first win at 26.2 miles may have contributed to that feeling A graduate of Utah State, she has run six marathons including the 2021 Boston Marathon, the 2023 Grandma's Marathon in Duluth, Minnesota, and the 2024 U.S. Olympic Team Trials in Orlando. She also won the 2023 Salt Lake City Half Marathon and the 2024 Hobble Creek Half Marathon. "There was so much woman support. Everyone kept me going with, 'Go girl! Go first woman! I love seeing the little girls cheering," Parkinson said. Dayton native and 2024 champion Olivia Anger was considered a pre-race favorite to break the tape, but she dropped out the day before the race. Parkinson's time is now the second-fastest women's winning time in race history. Anger previously held that title with a time of 2:43:22. Three-time winner Caitlin Keen has three of the top six winning times, all since 2018. The current trend suggests that Tatyana Pozdnyakova's course record of 2:34:33 could be broken in the near future. "I think women's marathoning is making huge progress right now. There's been a lot more research on what women need. Even for my own training, I feel like I'm understanding recovery a lot better and seeing improvements in my own running," Parkinson said. Parkinson turned her attention to her favorite post-race meal of street tacos, taking recommendations in the post-race huddle. She is also focused on qualifying for the 2028 Olympic Trials marathon. A site for that race is to be determined, but the Games of the XXXIV Olympiad will be in Los Angeles. She also has her eye on the New York City Marathon, which would be her third Abbott World Marathon Major after previously completing the Chicago and Boston marathons. "I have been dying to do that one day. I love east coast races," Parkinson said. Cincinnati native Daniella Townsend and Emma Bell, a recent high school graduate from Demotte, Indiana, were the next two placers, with Townsend in second (2:51:14) and Bell, third (2:52.12). Editor's note: This story has been updated with updated information from the Flying Pig Marathon. 11 CommentsPhil Parkinson says he is relishing a return to the Championship with Wrexham following the "complete and utter carnage" of his last stint in the division with Bolton Wanderers The Red Dragons sealed a third successive promotion last time out by beating Charlton Athletic 3-0 at the Stok Cae Ras to secure a return to the second tier for the first time since 1982 Having led Bolton into the Championship in 2017 and kept them in the division the following season amid turmoil at the club Parkinson was unable to keep the Trotters in the second tier for a second successive year Parkinson and assistant coach Steve Parkin departed the club in August 2019 after the club had been placed in administration but the Wrexham boss says he is looking forward to testing himself against a higher level of coaches again me and Steve that year we kept Bolton up was one of our greatest achievements of working together That was tough and then the summer," he told BBC Sport Wales "We actually started the next season well and then we had five months without getting paid I've never experienced anything like that "When people say about pressure and stress I always say working at Bolton and not getting paid for five months and trying to get a team motivated as a staff first of all we're looking forward to testing ourselves against a higher calibre of managers So we can't wait to test ourselves next year." Could Wrexham really reach the Premier League Wrexham's remarkable rise - and what comes next Club co-owners Ryan Reynolds and Rob McElhenney were both in attendance as Wrexham secured their all-important victory against Charlton Parkinson revealed he held talks with the Hollywood duo in the aftermath of the match in north Wales to reflect on the latest glorious chapter in the club's meteoric rise "I had a good chat with Rob after the game and on Sunday," added the Wrexham boss "Me and Ryan have exchanged quite a few messages this week and everyone's just reflecting "We were just reflecting on the occasion because for those people who were there at the weekend to seal Championship status and the whole atmosphere of the day is just something people won't forget "I'll never get bored of speaking to our supporters who were at the game." Wrexham sign off the 2024-25 campaign at Lincoln City on Saturday (15:00 BST) To load Comments you need to enable JavaScript in your browser View comments | 11Top storiesLive Alexander-Arnold to leave Liverpool & 'expected to join' Real Madrid - reaction and updates Alexander-Arnold to leave Liverpool at end of season 'Fire in my belly' led to team orders controversy The final series of Man Like Mobeen has arrived John Simm stars in the provocative 90s drama Warm-hearted comedy with Ben Miller and Sally Phillips Follow two ambitious river restoration projects Palmer's brilliance could be key moment in Chelsea's Champions League quest Europa League 'papering over cracks' for Man Utd - Rooney VideoEuropa League 'papering over cracks' for Man Utd - Rooney Ask Me Anything the new BBC Sport service designed to serve you Bayern's 'James Bond' - how Kane clinched his first trophy Nine bolters with a shot of making the Lions squad How 'absolutely outstanding' Palmer 'destroyed' Liverpool VideoHow 'absolutely outstanding' Palmer 'destroyed' Liverpool Still number one & 'sparring' with Draper - return of Sinner Saints 'punch' favourites Leinster in game for the ages How Bournemouth turned tables on set-piece specialists Arsenal VideoHow Bournemouth turned tables on set-piece specialists Arsenal Vardy the best £1m ever spent - Shearer VideoVardy the best £1m ever spent - Shearer 'Pretty special' - Leeds and Burnley's fight for Championship title Match-fixing scandal to Crucible final - fall and rise of Zhao Elton John & Happy Gilmore - McIlroy on Jimmy Fallon show 'Painful but we'll be back' - Luton's rise and fall 'Balls all over the Crucible floor' as pocket breaks during semi-final Video'Balls all over the Crucible floor' as pocket breaks during semi-final Two opposing views on football's transgender ban Varsho makes 'crazy' behind-the-back catch VideoVarsho makes 'crazy' behind-the-back catch Parkinson's disease (PD) is a neurodegenerative disorder in which the α-synuclein protein abnormally aggregates within brain cells researchers at KAIST have revealed that RNA editing plays a crucial role in regulating neuroinflammation a key pathology of Parkinson's disease and demonstrated that this mechanism is critically involved in the progression of Parkinson's disease Professor Choi's research team created a co-culture model composed of astrocytes and neurons derived from stem cells originating from Parkinson's disease patients in order to study the inflammatory responses of brain immune cells They then treated the model with α-synuclein aggregates which are known to cause Parkinson's disease and analyzed how the immune cells' inflammatory responses changed it was found that early pathological forms of α-synuclein which acts as a danger sensor in astrocytes as well as the interferon response pathway an immune signaling network that combats viruses and pathogens the RNA editing enzyme ADAR1 was expressed and transformed into an isoform with an altered protein structure and function Notably, the RNA editing activity of ADAR1, which normally functions to regulate immune responses during viral infections by converting adenosine (A) to inosine (I) through a process known as A-to-I RNA editing, was found to be abnormally focused on genes that cause inflammation rather than operating under normal conditions This phenomenon was observed not only in the patient-derived neuron models but also in postmortem brain tissues from actual Parkinson's disease patients This directly proves that the dysregulation of RNA editing induces chronic inflammatory responses in astrocytes ultimately leading to neuronal toxicity and pathological progression This study is significant in that it newly identified the regulation of RNA editing within astrocytes as a key mechanism behind neuroinflammatory responses it suggests that ADAR1 could serve as a novel genetic target for the treatment of Parkinson's disease It is also noteworthy that the study reflected actual pathological characteristics of patients by utilizing patient-specific induced pluripotent stem cell-based precision models for brain diseases This study demonstrates that the regulator of inflammation caused by protein aggregation operates at the new layer of RNA editing offering a completely different therapeutic strategy from existing approaches to Parkinson's disease treatment RNA editing technology could become an important turning point in the development of therapeutics for neuroinflammation." This study was published in Science Advances on April 11 with Professor Choi listed as a co-first author Paper Title: Astrocytic RNA editing regulates the host immune response to alpha-synuclein This research was supported by the Brain Research Program and the Excellent Young Researcher Program of the National Research Foundation of Korea as well as KAIST's Daekyo Cognitive Enhancement Program KAIST (Korea Advanced Institute of Science and Technology) D'Sa, K., et al. (2025). Astrocytic RNA editing regulates the host immune response to alpha-synuclein. Science Advances. doi.org/10.1126/sciadv.adp8504 Posted in: Medical Science News | Medical Research News | Medical Condition News Cancel reply to comment discusses how he is addressing today’s medical challenges using the technology of the future Explore how the Radian ASAP mass spectrometer is being used to streamline and enhance seized drug screening Mariangela Kosmopoulou and Tharan Srikumar Follow Bruker's experts as they discuss the SCRUM approach to software development in the scientific industry you can trust me to find commercial scientific answers from News-Medical.net please log into your AZoProfile account first Registered members can chat with Azthena, request quotations, download pdf's, brochures and subscribe to our related newsletter content A few things you need to know before we start Read the full Metrics details Parkinson’s disease is a progressive neurological disorder characterized by the degeneration of the nervous system leading to impaired motor and non-motor functions This study employs a multi-criteria decision-making approach integrating Fuzzy TOPSIS and Quantitative Structure–Property Relationship (QSPR) analysis to evaluate and rank 17 Parkinson’s disease medications based on their physicochemical properties Molecular structures were encoded as adjacency matrices using MATLAB 2017 and six Sombor index variants—computed via a custom Maple 2020 algorithm—served as topological descriptors for QSPR modeling Eight critical physicochemical properties were analyzed: polarizability (P) The Fuzzy TOPSIS ranking revealed bromocriptine as the top-performing drug for boiling point (BP) while comparative rankings across all properties are tabulated for clinical reference surface tension (ST) and polar surface area (PSA) showed weaker correlations (R2 < 0.5 highlighting limitations in their predictability via Sombor indices This work demonstrates the utility of combining chemical graph theory and Fuzzy TOPSIS for rational drug evaluation in neurodegenerative disorders The methodology offers a framework for prioritizing therapeutics based on physicochemical profiles with implications for optimizing Parkinson’s disease management these indices are instrumental in understanding the structure and function of DNA molecules and proteins topological indices play a pivotal role by predicting the efficacy and behavior of drugs based on the physicochemical characteristics of molecular structures We define the ve degree based Sombor index by replacing the classical degree of a vertex by ve degree The ve degree based Sombor index is defined as The ve degree based these variants of Sombor indices are defined as Finally conclusion section closes the article by providing insight the obtained results and future directions This study provides an innovative computational toolbox that can be crucial for modern biomedicine which is increasingly using data-driven approaches to untangle intricate biological and chemical systems This interdisciplinary methodology not only supports more informed drug selection but also exemplifies the computational applications in healthcare and medicine included calculations of regression parameters such as the correlation coefficient ($r$) and $p$-values Flow chart of the research methodology Chemical structures of anti-Parkinson drugs The physicochemical properties evaluated in this study are: A linear regression model was constructed using SPSS 29 statistical software with physicochemical properties as dependent variables and Sombor indices as predictors Model performance was rigorously assessed using the following metrics: Mean Squared Error (MSE): Quantifies the average squared difference between predicted and experimental values Mean Absolute Error (MAE): Measures the average absolute prediction error Coefficient of Determination ($r^{2}$): Indicates the proportion of variance in the dependent variable explained by the model p-value: Evaluates the statistical significance of each predictor (α = 0.05) Consistently low MSE and MAE values across most properties confirm the model’s robust predictive accuracy Statistically significant predictors (p < 0.05) are highlighted in the tables underscoring the utility of specific Sombor indices in modeling physicochemical behavior polar surface area (PSA) and surface tension (ST) exhibited poor predictability as indicated by their high p-values (p > 0.05) and low $r^{2}$ values (< 0.5) suggesting that these properties are not reliably correlated with the selected topological indices This discrepancy may reflect limitations in the structural descriptors or inherent complexity in the physicochemical interactions governing PSA and ST One of the particular benefits of the F-TOPSIS technique is its extremely user-friendly MCDM (Multi-Criteria Decision Making) approach; it can work effectively with a limited number of user-selected inputs (EI Alaoui The technique initially develops two important standards: the Positive Ideal Solution (PIS) and the Negative Ideal Solution (NIS) Choosing the option that is closest to the PIS and farthest from the NIS is the goal making this a practical and uncomplicated decision-making procedure the TOPSIS method underwent a significant change in 2000 with the introduction of the idea of F-TOPSIS By incorporating fuzzy logic and considerations into the conventional TOPSIS framework this addition gives the decision-making process an extra degree of flexibility and adaptability F-TOPSIS has been used in a variety of sectors where decision-making requires taking into account complicated and unpredictable data Before applying MCDM, we first scaled the drugs data given in Tables 1,2 and 3 using Z-score normalization where Z-score normalization is defined by Z = (X − μ)/σ σ is the standard deviation of the feature (column) criteria are classified into two categories: non-beneficial criteria and beneficial criteria Non-beneficial criteria are those where lower values indicate better performance These values are undesirable and required to be minimized the beneficial criteria are those where higher values indicate better performance These values are desirable and are needed to be maximized we assign weights to each performance criterion through the utilization of triangular fuzzy numbers we select appropriate linguistic variables for three decision-makers The evaluation is conducted based on different criteria for each decision-maker Step 3: The fuzzy weights ${\text{w}}_{\text{j}}$ of each criterion based on K decision makerscan be calculated using Formulas ${\text{w}}_{\text{j}}$ =(${\text{X}}_{\text{j}1}$ ${\text{X}}_{\text{j}2}$,${\text{X}}_{\text{j}3}$) where ${\text{X}}_{\text{j}1}={}_{\text{k}}{}^{\text{min}}{\{\text{X}}_{\text{j}1}^{\text{k}}\}$ ${\text{X}}_{\text{j}2}=\frac{1}{\text{K}}\sum_{\text{k}=1}^{\text{K}}{\{\text{X}}_{\text{j}2}^{\text{k}}\}$ ${\text{X}}_{\text{j}3}={}_{\text{k}}{}^{\text{max}}{\{\text{X}}_{\text{j}3}^{\text{k}}\}$ Before moving further,we first form a normalized matrix $\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{M} = \left( {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\mu }_{{{\text{ij}}}} } \right)_{{{\text{s}} \times {\text{t}}}}$ using initial matrix $\left( {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{X}_{{{\text{ij}}}} } \right)_{{{\text{s}} \times {\text{t}}}}$ where {i = 1,….s } is the number of experimental run and {j = 1 The normalization of performance criteria is done using the equation: Step 4: The weightage matrix is obtained by multiplying the normalized performance matrix by the associated aggregate fuzzy weights where $\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{M}_{{{\text{ij}}}} = {\text{T}}_{{{\text{j}}1}} \overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\mu }_{{{\text{ij}}}} ,{\text{T}}_{{{\text{j}}2}} \overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\mu }_{{{\text{ij}}}} ,{\text{T}}_{{{\text{j}}3}} \overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\mu }_{{{\text{ij}}}}$ Step 5: The Fuzzy positive Ideal solution and Fuzzy negative ideal solution are represented as $\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\frown}$}}{A} }_{{\text{j}}}^{ + }$ $\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\frown}$}}{A} }_{{\text{j}}}^{ - }$ and determine as Step 6: This step is required for defuzzification in order to turn evaluations into crisp theory This incorporates the Euclidean distance simplifications The Euclidean distance formula is written as where $\overbrace {d}^{{}}$ represents the distance between two fuzzy numbers and can be evaluated by the formula This provides the FPIS and FNIS in a crisp form This further simplify the distance formula as Step 7: The Closeness Coefficient $\widehat{{\text{CC}}_{\text{i}}}$ of the drugs which we have chosen here as alternatives can be determined as we sort your preferences in ascending order We select a quality desired with the highest $\widehat{{\text{CC}}_{\text{i}}}$ we explain each step of F-TOPSIS in detail The criteria that the decision-makers employ to assign a linguistic variable are as follows: The first decision maker (DM1) evaluates the quality of a regression model using the coefficient of determination ($r^{2}$) This metric indicates how well the independent variables explain the variance in the dependent variable where values closer to 1 signify a better fit linguistic variables are assigned for interpretability an $r^{2}$ value of 0.9 or higher is classified as Extremely High (EH) while an $r^{2}$ value of 0.01 or lower is labeled as Extremely Low (EL) Intermediate values are categorized as High (H) or Low (L) based on their proximity to these extremes DM1 prioritizes models with the highest $r^{2}$ ensuring that the selected drugs exhibit strong predictive power and explain most of the variability in the data The second decision maker (DM2) evaluates Mean Squared Error (MSE) as an indicator of model accuracy where lower values signify better predictive performance Since MSE values tending to zero are highly significant they are labeled as Extremely High (EH) in significance indicating a highly accurate model with minimal error an MSE close to 1 is considered Extremely Low (EL) in significance as it indicates substantial prediction errors or Low (L) significance levels based on their deviation from zero DM2 prioritizes models with the smallest MSE values ensuring precise predictions and minimal variability Now we assign triangular fuzzy integers using Table 10 we go to step 3 as already explained above we calculate fuzzy Significant weights ${\text{w}}_{\text{j}}$ of each criterion based on three decision makers using formulas we first form a normalized matrix $\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\text{M}} = \left( {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{\mu }_{{{\text{ij}}}} } \right)_{{{\text{s}} \times {\text{t}}}}$ using initial matrix $\left( {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\smile}$}}{X}_{{{\text{ij}}}} } \right)_{{{\text{s}} \times {\text{t}}}}$ by formula as shown in above steps More is Better (Benefit Criteria): Polarizability (P) Less is Better (Cost Criteria): Boiling Point (BP) we are going to evaluate Euclidean distance between two fuzzy numbers by the formula where $\overbrace {d}^{{}}$ represent distance between two fuzzy numbers.Table 10 represent the closeness coefficient $\widehat{{\text{CC}}_{\text{i}}}$ using formula below and hence we have FUZZY ranking Graphical representation of fuzzy ranking of anti-Parkinson drugs All data generated or analysed during this study are included in this published article and its supplementary files Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Primers 3, 17013. https://doi.org/10.1038/nrdp.2017.13 (2017) Olanow, C. W., Stocchi, F. & Lang, A. E. The scientific basis of current treatments for Parkinson’s disease. Annu. Rev. Med. 60, 103–116. https://doi.org/10.1146/annurev.med.60.042307.110802 (2009) Katzenschlager, R. et al. Mucuna pruriens in Parkinson’s disease: A double-blind clinical and pharmacological study. J. Neurol. Neurosurg. Psychiatry 74(12), 1736–1741. https://doi.org/10.1136/jnnp.74.12.1736 (2003) Surmeier, D. J., Obeso, J. A. & Halliday, G. M. Selective neuronal vulnerability in Parkinson disease. Nat. Rev. Neurosci. 18(2), 101–113. https://doi.org/10.1038/nrn.2016.178 (2017) Goedert, M., Spillantini, M. G. & Del Tredici, K. 100 years of Lewy pathology. Nat. Rev. Neurol. 9(1), 13–24. https://doi.org/10.1038/nrneurol.2012.242 (2013) Connolly, B. S. & Lang, A. E. Pharmacological treatment of Parkinson disease: A review. JAMA 311(16), 1670–1683. https://doi.org/10.1001/jama.2014.3654 (2014) Schapira, A. H. et al. Levodopa in the treatment of Parkinson’s disease: Current status and new developments. Euro. J. Neurol. 16(9), 982–989. https://doi.org/10.1111/j.1468-1331.2009.02760.x (2009) Stocchi, F., Rascol, O. & Destée, A. Early use of entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients: A 5-year study. Mov. Disord. 19(11), 1344–1350. https://doi.org/10.1002/mds.20218 (2004) Predictivepotential of eigenvalues-based graphical indices for determining thermodynamicproperties of polycyclic aromatic hydrocarbons with applications to polyacenes Hui, Z. H., Rauf, A., Naeem, M., Aslam, A. & Saleem, A. V. Quality testing analysis of Ve-degree based entropies by using benzene derivatives. Int. J. 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Res. 20(8), 889–899. https://doi.org/10.1016/0305-0548(93)90109-v (1993) Extensions of the TOPSIS for group decision-making under fuzzy environment Download references The authors really appreciated the kind support from the Research Supporting Project (RSP2025R401) Department of Natural Sciences and Humanities University of Engineering and Technology Lahore RCET College of Natural and Computational Science Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-025-99583-8 At the ARVO 2025 meeting in Salt Lake City Cameron Cummings presented a poster on how retinal microvascular imaging metrics may show sex-specific biomarkers for Parkinson's disease Editor's note: The below transcript has been lightly edited for clarity I'm a medical student at the Duke University School of Medicine and my project is on retinal structure and microvasculature in patients with Parkinson's disease and how it differs by sex Our lab and other labs have shown that retinal structure and microvasculature differ in Parkinson's disease regardless of sex and we know that Parkinson's disease presents differently in males and females that structural and microvasculature alterations might have So we had a cross sectional study where we had participants with Parkinson's disease and essentially found that comparing female controls with females with Parkinson's disease the females with Parkinson's disease had reduced perfusion density and vessel density in the 3mm circle and ring Those differences were not observed in males when we did the comparison between male controls and males with Parkinson's disease This led us to believe that the previously observed differences brought upon by Parkinson's disease may be primarily driven by females and we're hoping to do future work to figure out why that might be the case but it's possible that retinal microvasculature could be used as an early screening tool for Parkinson's disease We need to understand a lot more about it before it's used in any sort of diagnostic manner if there were to be OCT-A scans done as indicators of potential early Parkinson's disease our data suggests that diagnostic validity may be slightly more prominent in females such that if one were to use that criteria for males We would like to investigate hypotheses as to why our data looks the way it does Our current thinking is that it might have something to do with estrogen and its decline in menopause and during menopause it's obviously declines and we were thinking that it the decline may predispose females to microvascular damage by Parkinson's Don’t miss out—get Ophthalmology Times updates on the latest clinical advancements and expert interviews Subrata Batabyal, PhD, receives 2025 Carl Camras Translational Research Award from ARVO Foundation California dreaming: 2025 Glaucoma 360 brings celebration, innovation, and education to San Francisco Positive interim pilot clinical trial results of PKY-2101 Connect, learn, and innovate in a family-friendly atmosphere: What to expect at EnVision Summit 2025 OcuMet Beacon granted clearance by FDA Editorial Advisory Board members to present at Retina World Congress 2025 609-716-7777 Home / Raising awareness for Parkinson’s disease this April and highlight the importance of early detection and ongoing care we stand with our community in recognising the impact of Parkinson’s disease and reaffirm our commitment to providing compassionate Parkinson’s disease is a progressive neurological condition that affects the control of body movements It is the second most common neurodegenerative disease in Australia early diagnosis and access to appropriate medical and community support services can significantly improve quality of life our care teams work closely with patients and their families to manage the symptoms of Parkinson’s through a collaborative This may include support from neurologists social workers and nursing staff – each playing a crucial role in helping individuals live well with Parkinson’s “One in five are diagnosed before the age of 50 Research suggests the number of people living this multifaceted disease is increasing The disease affects the control of movement and various non-movement symptoms No two people with Parkinson’s disease have the same symptoms Common symptoms can include tremor when the limb is rested shuffling walking and mood changes,” says Dr Paul Kopanidis Parkinson’s disease is associated with an abnormal build-up of a protein in the brain called alpha-synuclein with accompanying loss of dopamine production Medications are important in the management to improve symptoms and quality of life as they can supplement the loss of dopamine “Currently we do not have a disease modifying drug to stop the disease exercise is a promising intervention to slow down the disease It is therefore important to build a team of clinicians to treat Parkinson’s disease,” adds A/Prof Doug Crompton and get involved in raising awareness this April For more information on Parkinson’s disease, support, education and links to research programs, please visit Fight Parkinson We acknowledge the traditional custodians of the land on which our health service is built those of the Taungurung and Wurundjeri people and we acknowledge their continuing connection to land the cultures and the Elders past and present A physician assistant specializing in Parkinson disease talked about how emerging technologies and proactive care models could transform the treatment landscape for Parkinson disease Telehealth has emerged as a pivotal tool in managing Parkinson disease (PD) offering patients increased access to specialized care particularly in underserved or rural areas Studies have demonstrated that telemedicine can deliver clinical outcomes comparable to in-person visits and enhance patient satisfaction and reducing travel burdens.1 Moreover coordinated telehealth programs encompassing speech therapy and pharmaceutical care have proven feasible and safe indicating potential efficacy for individuals with PD residing in remote communities.2 These advancements underscore telehealth's role in providing efficient and patient-centered long-term care for those living with PD As telehealth expands the reach of PD care including nurse practitioners and physician assistants are playing an increasingly vital role in delivering and coordinating that care and strengthens multidisciplinary collaboration particularly in settings with limited access to movement disorder specialists.3 APPs are known to be well-positioned to conduct telehealth assessments making them potentially essential to meet the growing demand for high-quality PD care Recently, NeurologyLive® sat down with Cheryl Kyinn, PA-C to discuss the evolving role of technology and patient engagement in managing the movement disorder she emphasized the shift from limited symptom management to a future focused on disease modification through gene and stem cell therapies as well as underscored the importance of wearable devices and remote DBS programming in enhancing patient accountability and access to care Kyinn stressed the critical role advanced practice providers can play in addressing the growing demand for specialized care amid a provider shortage Nexalin Initiates Q-Submission Process for Transcranial Alternating Current Stimulation Device in Alzheimer Studies Episode 140: Down Syndrome and Alzheimer’s: Clinical Trials, Equity, and Patient-Centered Progress Evolving Clinical Insights Into Neuroimmune Mechanisms and Multiple Sclerosis Progression Episode 139: Sleep and Seizures: Emerging Insights From AAN 2025 From Sickle Cell to Stroke Prevention: Robert J. Adams’ Leadership in Brain Health Equity Transforming Neurological Care Delivery: Barbara Vickrey’s SEQUINS Hall of Fame Journey a natural compound found in certain mushrooms has shown promise in treating depression and anxiety UC San Francisco researchers wanted to know if it could be used to help Parkinson’s patients who often experience debilitating mood dysfunction in addition to their motor symptoms and don’t respond well to antidepressants or other medications Not only did participants tolerate the drug without serious side effects or worsening symptoms which is what the pilot study was designed to test they also experienced clinically significant improvements in mood and motor function that lasted for weeks after the drug was out of their systems It is the first time a psychedelic has been tested on patients with any neurodegenerative disease “We are still in very early stages of this work, but this first study went well beyond what we expected,” said the paper’s first author, Ellen Bradley, MD, assistant professor and associate director of UCSF’s Translational Psychedelic Research Program (TrPR) but mood symptoms in Parkinson’s are linked to a faster physical decline,” she said “And they are actually a stronger predictor of patients’ quality of life with Parkinson’s than their motor symptoms.” Researchers in the TrPR Program, within UCSF’s Department of Psychiatry and Behavioral Sciences and the Department of Neurology, teamed up to lead this project, which was funded by an anonymous donor. The findings appeared online earlier this month in Neuropsychopharmacology a progressive neurodegenerative disorder characterized by uncontrolled movements due to abnormal brain activity While medications like levodopa can relieve symptoms there are no approved therapies to slow the progression or reverse the disease itself Common early physical symptoms include tremors and foot dragging but Bradley said anxiety and depression in patients with no history of psychiatric problems often precede the onset of motor symptoms by several years It’s unclear why standard medications often don’t work well for these patients but mood changes could be part of the neurodegenerative disease process To test the safety of psilocybin for these patients the researchers gave seven men and five women with mild to moderate Parkinson’s disease a 10 mg dose followed two weeks later by a higher dose of 25 mg The patients completed psychotherapy sessions before and after the psilocybin — eight sessions in total — and were evaluated for changes in mood While nearly all participants experienced some adverse events while on the psilocybin these were not serious enough to require medical intervention The participants had meaningful improvements in their mood and motor symptoms at both their one-week and one-month follow-up appointments The team evaluated the participants’ mood again three months after their psilocybin sessions and found it was still significantly improved The researchers suggested a variety of explanations for the improvements The beneficial impact of psilocybin on the patients’ mood could have led to better cognitive and motor functions helps them socialize and become more active – both key elements of Parkinson’s treatment Another theory is that psilocybin could provide relief from multiple symptoms of the disease by reducing inflammation and promoting neuroplasticity – the growth and reconnection of brain cells involved in mood The results of this pilot study were promising enough that the researchers are conducting a larger randomized controlled trial at UCSF enrolling a larger and more diverse group of patients The second study incorporates noninvasive brain stimulation neuroimaging and other tools to understand how psilocybin impacts inflammation and neuroplasticity It will include a second site at Yale University with the aim of enrolling 100 participants This work will be funded by the same anonymous donor that paid for the safety pilot as well as by the Michael J “The vast majority of brain diseases still lack interventions that change the course of illness,” said the study’s senior author, Joshua Woolley associate professor at UCSF and director of the TrPR Program Authors: Additional co-authors include Kimberly Sakai Funding: The trial was funded by an anonymous donor Subscribe to UCSF News Visit the Media Center © 2025 The Regents of The University of California Metrics details Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson’s disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial (NCT01898390) was designed to determine whether this approach could be further developed into a clinically useful treatment Owing to poor availability of human fetal ventral mesencephalic tissue only 11 individuals were grafted at two centers using the same tissue preparation protocol but different implantation devices No overall clinical effect was seen for the primary endpoint 3 years after grafting No major graft-induced dyskinesias were seen but we observed differences in outcome related to transplant device and/or site Mean dopamine uptake improved at 18 months in seven individuals according to [18F]fluorodopa positron emission tomography imaging but was restored to near-normal levels in only one individual Our findings highlight the need for a stem cell source of dopamine neurons for potential Parkinson’s disease cell therapy and provide critical insights into how such clinical studies should be approached there has been much interest in replacing the lost A9 dopaminergic nigral neurons in PD through transplants of similar cells most notably the developing dopaminergic neural precursor cells derived from the human fetal ventral mesencephalon (hfVM) collected after planned termination of pregnancies This group served as a control group against which to compare our grafted patient cohort Predefined secondary measures were examined along with PET imaging that investigated dopaminergic and serotonergic markers we found no obvious benefit from the hfVM transplants across the grafted cohort comparing against their baseline values and against the nongrafted natural history control group evidence of a positive correlation between clinical effect and number of surviving hfVM-derived dopamine cells as evident in changes in dopaminergic PET imaging there were differences in outcomes between the surgical sites which may relate to the device used to deliver the cells given that the tissue preparation was standardized between centers changes were seen after grafting on [11C]3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]DASB) PET imaging and in three patients nondisabling GIDs were observed The basic demographics of the transplant and control patient cohorts are presented in Table 1 Thirty-six individuals were randomized to join the transplant arm of the study but nine withdrew during the prerandomization assessment and 16 remained as nongrafted PET ‘control’ individuals No patients were excluded because of significant ventral striatal 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine ([18F]FDOPA) loss and all 11 patients approached for grafting after baseline imaging consented and were enrolled with the exception of 1 who did not wish to be treated with immunosuppressive drugs Change in motor UPDRS (UPDRS Part III) in defined OFF state at 36 months after last transplantation (OFF being defined as receiving no dopamine therapy for 12 h before the assessment or longer in the case of long-acting dopamine agonists (for example Change in timed motor tasks at 36 months after transplantation Change in l-DOPA equivalent daily dose at 36 months after transplantation Number of patients on l-DOPA therapy at 36 months after transplantation Change in patient-reported OFF time at 36 months after transplantation Change in quality of life outcome measures as reported by the patient (Parkinson’s Disease Questionnaire-39 (PDQ-39)) Changes in [18F]FDOPA PET in transplanted patients 36 months after transplantation a, Individual trajectories. Time since entering the study was mean centered for the control individuals to align the x axes with the transplanted group. b,c, Average change per month by group (b) and device used (c). The green arrow indicates patient 79, and the brown arrow corresponds to patient 60 with near normalization on their dopamine PET scans. Results of mixed two-way analyses of covariance (ANCOVAs) for bilateral putamen [18F]FDOPA Ki (a; P = 0.066) and [11C]PE2I BPND (d; P = 0.000062) including group (transplant: n = 8; control: n = 16) and visit (before transplant (Pre-Tx)/baseline and after transplant (Post-Tx)/18-month follow-up (18m FU) for transplant/control groups adjusting for mean-centered age at baseline Results of two-way repeated measures ANCOVAs within the transplant group (n = 8) are also shown for [18F]FDOPA Ki (b; P = 0.025) and [11C]PE2I BPND (e; P = 0.000057) Strip plots illustrate two-way interactions between region (bilateral putamen and caudate) and visit (baseline adjusting for mean-centered age and disease duration at baseline Bootstrapped means and 95% confidence intervals (bias-corrected and accelerated procedure 10,000 replicates) by surgical device (TRN3/TRN4/R–L/control) and visit (before transplant/baseline and after transplant/18-month follow-up for transplant/control respectively) were generated considering data from all putamen unilaterally and plotted for both [18F]FDOPA Ki (c; device n = 5 (TRN3) and 32 (control)) and [11C]PE2I BPND (f; device n = 4 (TRN3) Partially transparent lines represent data from individuals whereas opaque lines and error bars represent estimated marginal means and 95% confidence intervals Dotted horizontal lines for putamenal [18F]FDOPA Ki (a–c) represent the lower bound (pooled mean – 2 s.d.) for a healthy older cohort (n = 6 studies; total n = 71) Significance was analyzed by Tukey-adjusted post hoc tests; *P < 0.05; **P < 0.01; ***P < 0.001 (two sided); Ct A large number of secondary measures were examined. The largest changes were seen in the l-DOPA equivalent daily dose and the percentage of time patients reported being in the OFF state (Table 2) patients who were transplanted had better outcomes than control individuals namely lower l-DOPA equivalent daily dose and reduced time in the OFF state We report specifically on changes in the equivalent doses of l-DOPA medication taken at the end of the trial compared to just before their first transplant to determine whether graft implantation lowered their requirements for such medication bootstrapped means and 95% confidence intervals suggested that the most affected side of the putamen ([18F]FDOPA Ki: 0.0047 (0.0044 2.29)) responded better to surgery than did the least affected side ([18F]FDOPA Ki: 0.0055 (0.0048 the responses of the putamen transplanted first ([18F]FDOPA Ki: 0.0050 (0.0045 2.10)) compared to those of the putamen transplanted second ([18F]FDOPA Ki: 0.0052 (0.0046 Representative [18F]FDOPA (left) and [11C]PE2I (right) parametric images for two bilaterally transplanted patients whose postoperative levels of dopamine synthesis and transporter expression were either high (patient 60) or comparatively modest (patient 54) Dopaminergic PET data are overlaid onto patient T1-weighted magnetization prepared rapid gradient echo (MPRAGE) scans rigidly aligned to the Montreal Neurological Institute (MNI) template and displayed as axial slices covering the putamen; R Compared to the patients in our previous studies with fetal grafts (Lund series: patients 3–10 and 12–16; Supplementary Table 1) both the postoperative [18F]FDOPA Ki increases relative to normal and the percentage [18F]FDOPA Ki change relative to before the operation were substantially lower in the TransEuro group (3.22 versus 20.84% and 6.92 versus 70.43% The amount of implanted tissue did not differ significantly between the groups the tissue implanted in the TransEuro patients had been exposed to tirilazad mesylate to improve the survival of grafted dopaminergic neurons Despite the amount of implanted tissue being similar in these groups the postoperative [18F]FDOPA Ki increases relative to normal and the percentage [18F]FDOPA Ki change compared to before the operation were much higher in the previously grafted patients (17.28 and 62.83% These data were also evaluated after Box–Cox transformation given the mild leptokurtic residual distribution but results were similar using the untransformed data Two hundred and sixty five of the 430 recorded adverse events (61.6%) in the transplant group related to a nonclinically significant abnormal investigation result These mainly related to blood test results in the postsurgical setting The transplant arm also underwent a much more intensive visit and investigative schedule than the control arm particularly with regular postsurgery safety visits where blood tests were performed and adverse events were recorded No abnormal investigation results were recorded for the control group as these patients did not have routine blood monitoring as part of their participation in the TransEuro trial As the neurological adverse events were much higher in the transplant group than in the control group there were 37 neurological adverse events among nine patients of whom seven had at least 1 adverse event that was related to worsening parkinsonism This tended to occur in the immediate postoperative procedure as is typically seen in patients with PD undergoing major surgery with a general anesthetic Three patients developed what seemed to be dyskinesia in the OFF state which are assumed to be GIDs; in all cases they were mild and not disabling Six patients who were grafted had at least one other neurological adverse event (there were two intracerebral hemorrhages that resulted in no neurological sequelae) there were only four neurological adverse events documented in the control group two of which were related to PD (increased OFF period time and worsening freezing) Five of the 11 (45.5%) patients in the transplant arm and 3 of the 16 (18.8%) patients in the control arm had serious adverse events totaling seven and five serious adverse events There were no deaths among either the control or transplant participants of the study Five of the seven serious adverse events in the transplant group were deemed to be related to the transplant procedure or immunosuppression (Supplementary Table 4) Three were procedure related (two intracerebral hemorrhages and one wound dehiscence) and two were related to immunosuppression (azathioprine-induced colitis requiring hospital admission and a Kaposi’s sarcoma both of which resolved on modifying the immunosuppression) The intracerebral hemorrhages were detected 2 days after surgery on routine scans One (in a patient undergoing surgery in Lund) which was located in the immediate vicinity of the burr hole and thought to relate to diathermy of bridging veins caused minor symptoms that resolved within 2 weeks the hemorrhage was intraparenchymal and above the transplant site but was asymptomatic Intracerebral hemorrhage has a 1% risk with any intracerebral procedure and if we assume an independent 1% risk of hemorrhage per needle pass then the occurrence of two hemorrhages in 105 needle passes in this study is not that unexpected None of these severe adverse events resulted in long-term disability although one did result in a transplant patient having to discontinue all immunosuppression before the planned 12-month time period One patient (patient 79) had both their transplants placed outside the target site with both grafts placed laterally to the striatum The major targeting error in this patient was in the y axis rather than the z axis which would have been the case if there was a depth miscalculation relating to the device There was also no calibration error in the stereotactic frame used The trial was temporarily suspended when this was seen on the day 2 postoperative magnetic resonance imaging (MRI) scan following the first transplant and another from a separate independent neurosurgical center met to discuss the case and look at all the relevant information and imaging No obvious explanation could be given for this and the same graft misplacement happened when the patient was grafted on the contralateral side This misplacement of grafts was incorporated into the data analysis and highlighted in the plotted data and was not seen in any other patient This analysis formed the basis for the design of the TransEuro trial Our evidence from the current trial clearly indicates that transplantation of hfVM tissue is not a clinically feasible therapeutic strategy for patients with PD we show that despite major efforts from two collaborating centers access to hfVM tissue is insufficient to allow for scheduling clinical transplantations many planned surgeries in the TransEuro trial had to be canceled our use of a simple randomization approach for patient allocation to the transplant versus control arms may have led to problems in balancing the two groups despite standardized dissections and tissue preparations variation in the gestational age of the donors for each patient the shortage of tissue available for each patient and the limited possibilities for standardization and quality control inherently lead to variation in outcome only one of eight bilaterally grafted PET-imaged patients showed near-normal levels of putamenal dopaminergic innervation This low efficacy in restoring putamenal dopaminergic signaling which forms the mechanistic basis for a potential motor improvement the trial did not reveal any significant clinical benefit in the group of grafted patients compared to controls we observed differences in the degree of restoration of putamenal dopamine levels between the two centers which used different surgical devices but the same amount of implanted tissue (three hfVMs per putamen) This illustrates that surgical and device-related issues can significantly influence the outcome after transplantation of hfVM tissue all were mild and did not require additional neurosurgical interventions to treat them We did see some evidence that the implantation of hfVM tissue may have improved the clinical trajectory of treated PD when comparing pre- and postintervention scores in patients who received a graft and when comparing to a contemporary natural history control population of individuals with PD occurred in only seven individuals and slowly emerged over time suggesting that it was unlikely to be a placebo effect We sought to minimize investigator bias in the assessment of patients by comparing the similarity of scores using a blinded third rater who scored patient videos coupled to the imaging data on dopamine innervation at the site of grafting further support the belief that the clinical response was due to surviving implanted dopaminergic neurons This is also in line with the fact that both l-DOPA equivalent daily dose (LEDD) and reported OFF times were lower in grafted patients 36 months after surgery than in the natural history control individuals We found no consistent major placebo effect associated with long-term follow-up (reinforced by a complete absence of clear clinical or imaging effects in a patient in which the tissue was not grafted into the correct target region) we eventually ended up producing a smaller the interpretation of the data is limited given that only 21 transplants were performed in 11 patients over a 3-year period and thus any conclusions we draw have to be seen as tentative and more anecdotal than definitive This is especially the case given the limited long-term PET scanning we could complete because of restrictions related to the coronavirus disease 2019 (COVID-19) pandemic The use of stem cells also gives the possibility to exclude serotonergic neurons and their progenitors which is not feasible using fetal tissue where these two cell populations reside in close proximity other factors seemed to also contribute to the variability in our study including the center where surgery was performed This implicates factors such as patient selection neurosurgical approach and tissue preparation which we endeavored to standardize but we were ultimately unable to use the same device at the two surgical sites The original aim to use the R–L device in both Lund and Cambridge was not possible as the device is not Conformité Européenne marked and thus could only be used in the hospital where it was made (Lund) An imitation device had to be manufactured at the Cambridge site based on the original R–L instrument but it was clearly not identical and may have explained some of the between-site differences in outcome the patients that were randomly selected for surgery out of the observational study at the two sites had slightly different baseline characteristics with patients in Lund having slightly less advanced disease This may account for the differences by site less advanced patients have better outcomes the small numbers of patients prevent any formal analysis of this hypothesis we now assess all patients jointly across centers before transplantation to ensure that baseline characteristics are more comparable Although overall the approach was well tolerated it was not without complications with respect to surgical procedure and immunosuppression There were two intracerebral hemorrhages (without any lasting neurological sequelae) and two patients developed complications with their immunosuppressive drugs that necessitated stopping some of the agents they were taking This is a relatively high rate of complications although ultimately none were disabling or caused major long-term problems for the patients This level of complication may relate to the novelty of the approach and with time would likely lessen if the technique became more widely adopted as was the case for deep brain stimulation for PD this will be an important area to monitor as the newer stem cell dopamine cell therapies are tested in trials stem cell therapies may have another advantage in that they will lack 5-HT contaminants We sought to reduce the risk of GIDs by minimizing the level of 5-HT contamination within our grafted tissue using a restricted dissection approach but this proved inadequate as evidenced by changes in 5-HT innervation after grafting long run-in periods of patients who are then grafted the use of PET imaging to monitor dopamine cell survival and innervation density and contemporaneous natural history controls have all been shown to be valuable in assessing the safety and efficacy of such interventions and should be considered in all future stem cell-derived dopaminergic neuron therapy trials ensuring that sufficient numbers of dopamine cells survive long term and innervate the transplant site such that the dopamine innervation within the grafted striatum is restored to normal Relevant factors that we have identified here include the dose of cells implanted the device used for delivery of the cell product and possibly age of the patients (that is the TransEuro trial has provided insights not only in trial design but also in some of the critical factors that need to be taken into account in the new round of stem cell-based dopamine cell replacement trials in patients with PD Thirty-six patients were recruited into the transplant trial and randomly allocated to the transplant arm of the study or the control arm These patients underwent the same PET and clinical examinations as the transplant arm but did not receive immunosuppression and did not undergo sham surgery Ethical permission was received for fetal tissue preparation and use at Cambridge (96/085) Cardiff (13/WA/0210ADD) and Lund (2013/432 and 2016/535) The transplant study was approved by the relevant ethical authorities in the United Kingdom and Sweden (REC reference number 10/H0304/77 in the United Kingdom and the Swedish Ethical Review Authority (Etikprövningsmyndigheten) in Lund (reference numbers 2011/290 The original study design was to transplant 20 patients in an open-label fashion drawn from a larger natural history cohort of 150 participants and the data obtained would then be used to calculate sample size needed for a larger double-blind placebo-controled trial All of this was to be done over a 5-year period a decision was made to stop the transplant trial when either all 20 patients had been grafted or 3 years had elapsed from the time of the first transplant This decision was based on the following reasons: it seemed unethical to prolong the study beyond this time as it was clearly showing that using this tissue source in a trial was not feasible in the United Kingdom and Sweden interpretation of the study would become extremely difficult if some patients had already reached their primary endpoint whereas others had still not been grafted advances in human stem cell-derived dopamine cells meant that trials using this new source of more readily available cells were already entering the clinic24 the time of the final data collection for our predefined primary endpoint for the last patient was in March 2021 Collection of the follow-up clinical and PET imaging data was delayed (and in some cases not possible) because of restrictions resulting from the COVID-19 pandemic that began in March 2020 and this included the 36-month PET imaging in the majority of patients To try and standardize the timings to better align with the PET imaging analysis we defined a pretransplant baseline as the visit immediately before the first transplant We then elected to use the following as the key time points for the primary and secondary outcomes: 18 months: first visit at least 510 days after the last transplant surgery or after the baseline visit (control; 540 days = 30 × 18 months with 30 days leeway) 36 months: first visit at least 1,020 days after surgery (transplant) or after the baseline visit (control; 1,080 days = 30 × 36 months with 60 days leeway) Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Cambridge MRI and PET scanning were performed at Invicro Patients had a structural MRI and [11C]PE2I [11C]DASB and [18F]FDOPA PET scans at baseline and repeat scans just before surgery and at 18 months after their first transplant The planned 36-month scanning could not be performed in sufficient numbers of patients because of the COVID-19 pandemic that began in 2020 Cerebellar gray matter was isolated using DARTEL to estimate flow fields from the MNI template to native space applying this to CIC Atlas v1.2 and masking with a gray matter segment Dynamic PET images were motion corrected and co-registered with their corresponding MPRAGE using the summed PET images as an intermediary and normalized mutual information as a cost function Parcellations were then applied to the dynamic PET data to generate regional time–activity curves Patlak graphical analysis was used to quantify the uptake rate constant (Ki) Logan graphical analysis was used to quantify BPND BPND was estimated with Simplified Reference Tissue Model 2 (SRTM2) Cerebellar gray matter was used as a reference region for all tracers Transplanted tissue was prepared from hfVM dissected from three fetuses collected after either medical or surgical abortions under full ethical approval. Tissue dissections were standardized across centers by established landmarks and documentation of each cut using photographs. The landmarks used for dissection are shown in Supplementary Fig. 1 The collected tissue was stored for a maximum of 4 days in Hib(E) at 4 °C three hfVMs were pooled and washed several times in DMEM (cGMP compliant A12861 01)/tirilazad mesylate (custom made to GMP grade The hfVMs were enzymatically digested in a mixture of Tryple E CTS (cGMP compliant Life Technologies A12859-01) and Pulmozyme (Dornase-α the tissue was washed three to four times in dissociation medium DMEM/tirilazad mesylate/dornase-α to remove any Tryple E residue The hfVMs were then dissociated very gently to produce a crude cell suspension Aliquots of 5 × 20 µl were prepared after confirmation of viability and transported to theater in a temperature-monitored cool box Quality criteria to proceed with transplantation of hfVM cells was set at >80% cell viability on the day of implantation Although insufficient tissue was a common problem given that the cell preparation had to be derived from at least three hfVMs per side grafted only one cell preparation had a viability below that required for surgery The crown rump length of the fetus varied between 15 mm (gestational age (weeks ± days) 7 + 6) and 35 mm (gestational age 10 + 2) and the final cell suspension viability was between 83 and 93% This may also have had an impact on the final number of surviving dopaminergic cells within the graft as might the time spent in hibernation media before the final tissue preparation and transplant surgery an in-house-manufactured version of this device was made (TRN3) which was subsequently modified (TRN4) part way through the trial This modification was undertaken in response to feedback from the neurosurgeon using the device in Cambridge and the needle in both devices had an internal diameter of 0.82 mm and an external diameter of 1.07 mm patients were given prophylactic antibiotics and were started on a standard whole-organ immunosuppressant regimen of cyclosporin (titrated to serum levels of between 100 ng ml–1 and 200 ng ml–1) 2 mg per kg (body weight) per day azathioprine and 40 mg of prednisolone weaning to 5 mg over 12 weeks after a one-off dose of 1 g at the time of surgery Immunotherapy was maintained for 12 months after the last transplant and was then stopped patients also took all recommended prophylactic treatments for patients on this immunosuppressive regimen calcichew daily and alendronic acid once a week 24 and 48 h after surgery for routine postsurgical observations and blood tests a postoperative brain MRI scan was performed to verify graft placement and examined for any perioperative hemorrhage In addition to their regular study clinical assessment visits 9 and 12 months after surgery as well as blood testing to monitor their immunosuppression The primary outcome measure was defined as change in the UPDRS Part III score in the defined OFF state at 36 months after surgery compared to baseline a motor score was felt to be the most appropriate measure and the 36-month time point was chosen to allow sufficient time for any post-transplant benefits to evolve Secondary outcomes included a range of motor quality of life and cognitive measures as well as changes in dopaminergic medication site to site variability and procedural and patient heterogeneity it is debatable whether inferential analyses are relevant and interpretable no inferential statistics were used to assess the efficacy of the transplants on the primary or secondary outcomes Statistical analysis of the imaging data included all bilaterally transplanted patients who completed the multi-PET protocol at three time points (n = 8) We performed two-way mixed ANCOVAs with repeated measures to examine whether differences in mean putamenal [18F]FDOPA Ki [11C]PE2I BPND and [11C]DASB BPND values depended on group (transplant or control) and visit Visit included pretransplant and 18 months post-transplant time points for the transplant group (n = 8) or baseline and 18-month follow-up time points for the control group for which data were available for 16 patients for [18F]FDOPA Ki and [11C]PE2I BPND and for 14 patients for [11C]DASB BPND We also conducted a series of two-way repeated measures ANCOVAs to examine whether differences in mean striatal [18F]FDOPA Ki [11C]PE2I BPND and [11C]DASB BPND values depended on visit (baseline pretransplant and post-transplant) and striatal region (putamen and caudate) The caudate was included as an internal control region given that it is also known to exhibit substantial dopaminergic neurodegeneration over time in PD mean-centered age and disease duration at the first included time point were entered as continuous covariates where possible as they have been shown to be related to dopaminergic and serotonergic loss Post hoc Tukey-adjusted pairwise comparisons of the estimated marginal means were conducted to evaluate pairwise differences where appropriate Spearman’s rank-order correlations were conducted to evaluate the relationship between the changes in PET parameters (posttransplant–pretransplant) and primary and secondary outcome scale change scores observational data collected closest in time to the PET acquisitions were included for analysis Statistical analyses and visualizations were computed in R version 4.2.2 using the following packages: afex 1.3.0 Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Data that support the findings of this study are not openly available to protect study participants’ privacy Data may be requested from the corresponding author upon reasonable request immediately and for a period of 36 months following article publication Reasonable requests will be considered from researchers who provide a methodologically sound proposal Study documentation, including the protocol and statistical analysis plan, is available within the Supplementary Information Improving the delivery of levodopa in Parkinson’s disease: a review of 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Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease iPS cell-based therapy for Parkinson’s disease: a Kyoto trial Molecular imaging and kinetic analysis toolbox (MIAKAT)—a quantitative software package for the analysis of PET neuroimaging data Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease A detailed account of methodology and a 6-month follow-up Download references We would like to thank the following funding for this trial: EU FP7 grant (242003) Cure Parkinson’s (RG81537) and John Black Charitable Trust and Multipark is also a principal investigator in the MRC/WT Stem Cell Institute (203151/Z/16/Z) by the Wellcome Trust (203151/Z/16/Z and 203151/A/16/Z) and the UKRI Medical Research Council (MC_PC_17230 and MR/P025870/1) the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission This research was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312) The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care the trial in Lund was supported by the Agreement for Medical research and Education (ALF) Lund University and the Wallenberg Center for Molecular Medicine The research leading to these results has received funding from the New York Stem Cell Foundation (NYSCF-R-I37) the Swedish Research Council (2016-00873 and 2021-00661) The Swedish Parkinson’s Association (Parkinsonfonden) the Swedish Brain Foundation (Hjärnfonden FO2019-0301) and the Strategic Research Area at Lund University MultiPark (Multidisciplinary Research in Parkinson’s Disease) infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre and the NIHR Imperial CRF The views expressed are those of the authors and not necessarily those of the funder has received financial support through a PhD studentship awarded by Parkinson’s UK Van Andel Research Institute and Defeat MSA Cardiff fetal tissue bank was supported by the following grant: Quality assured human fetal tissue for biomedical research and clinical trial in neurodegenerative disease Clatworthy for help in aspects of the immunotherapy management in some of the transplanted Cambridge patients We would also like to thank the staff at Invicro for their support with the PET imaging we would like to give our sincere thanks to the patients and their families for their incredible dedication and support to this trial and the people working within it Department of Clinical Neurosciences and Cambridge Stem Cell Institute Andreas-Antonios Roussakis & Paola Piccini Department of Clinical & Movement Neurosciences Skånes University Hospital and Lund University Division of Psychological Medicine and Clinical Neurosciences Lund Stem Cell Center and Division of Neurology All authors contributed to trial set up and execution along with data collection The following wrote the first draft of this manuscript: R.A.B. All authors critically read the manuscript and offered feedback Analysis of the data was primarily undertaken by N.P.L.-K. Imaging data were provided primarily by N.P.L.-K Principal investigators at each site: University of Cambridge Nature Biotechnology thanks Jeffrey Kordower and the other reviewer(s) for their contribution to the peer review of this work Download citation DOI: https://doi.org/10.1038/s41587-025-02567-2 A revolutionary new study will examine whether environmental toxins could lead to the onset of Parkinson’s Disease Professor Ooi will examine how the onset and development of Parkinson’s Disease could be influenced by the exposure levels of a range of different toxins from chemicals used in industrial settings to those in the domestic sphere Parkinson’s Disease is the fastest growing neurological condition in the world and is second in Australia only to dementia degenerative neurological condition that affects a person’s control of their body movements. There are more than 150,000 people living with Parkinson’s Disease in Australia Professor Ooi said the funding will allow the research team to delve deeply into the fascinating relationship between exposure to environmental pollution and the risk of disease a connection that has long been suspected in Parkinson’s “There are many culprits that contribute to the development of neurological conditions and it can be incredibly difficult to isolate any one culprit Many of the toxins we will investigate are found in the environment these impact our long-term health,” Professor Ooi said “If we understand how the toxins contribute to Parkinson’s we can learn how to potentially prevent this devastating disease.” the team is reprogramming regular human cells into the specific brain cells that are affected by Parkinson’s support cells that play vital roles in protecting neurons – are both types that are progressively lost in Parkinson's which includes Associate Professor Shane Ellis will then use these cells to examine the impact of environmental toxins on the debilitating neurological condition "This approach allows us to directly observe how these toxins affect the brain cells involved in Parkinson's disease," said Professor Ooi "By exposing brain cells to these substances we can analyse the resulting changes in cellular chemistry and identify 'metabolic signatures' – unique molecular patterns that indicate damage related to Parkinson's." said: “This research has the potential to provide critical insights into potential preventative measures and treatment options for Parkinson's disease By understanding the environmental factors that contribute to the disease we can work towards developing strategies to mitigate their impact.” Dr Paul Di Pietro UOW Interim Deputy Vice-Chancellor and Vice-President (Research and Sustainable Futures) congratulated Professor Ooi and the team on the prestigious grant “The work of exploring what causes diseases is long and painstaking but the findings have a tangible impact on the lives of others This study will play a critical role in advancing our understanding of Parkinson’s Disease and reflects the remarkable research capacity and capability of Professor Ooi and her team,” he said Northfields Ave Wollongong, NSW 2522 Australia Phone: 1300 367 869 International: +61 2 4221 3218 Switchboard: +61 2 4221 3555 we acknowledge and respect the traditional custodians and cultural knowledge holders of these lands Copyright © 2025 University of WollongongCRICOS Provider No: 00102E | TEQSA Provider ID: PRV12062 | ABN: 61 060 567 686Copyright & disclaimer | Privacy & cookie usage | Web Accessibility Statement Add articles to your saved list and come back to them any time They met doing advocacy work and have been dating for almost a year “We’d both had a really shitty time with our disease before we met and now appreciate good times,” says Tinkler.Credit: Dominic Lorrimer Emma: I’d known Martin for a week when I asked him to come to a neurology appointment with me in May last year It’s always good to have another pair of ears when you see a specialist They always ask about your bowel movements at these appointments but I felt totally comfortable discussing that in front of him he texted me saying he was coming to my apartment via a patisserie I’ve gone too far too early.” Then he texted back He made us a shared Spotify playlist and said “I love you” after two weeks We’d both had a really shitty time with our disease before we met and now appreciate good times No couple ever knows what’s around the corner but having Parkinson’s brings up a lot of what-ifs I try not to think about it too much because I can go to a dark place we were cuddling in bed when I thought about us together as old people and started to cry People with late-stage Parkinson’s have a higher chance of developing dementia and I was picturing two old ‘We never get the shits with each other about this stuff because we know how it feels.’ There are bad days but also bad hours; it can change in minutes If my gait is slow or it feels as if my body’s tightening from the inside and I don’t have the bandwidth for a proper conversation while I’m dealing with symptoms We were leaving in 15 minutes to go to a party when I told him I didn’t think I’d be able to get there because my meds weren’t kicking in and I felt as if I had weights on my wrists and ankles We never get the shits with each other about this stuff because we know how it feels Can you grab my phone?” Or when he’s having difficulty putting his socks on – one of the symptoms is a loss of dexterity in your fingers – I help him He found it difficult to receive help at first because he’s been so independent Together, we’re trying to raise awareness of how many younger people get Parkinson’s [April is Parkinson’s Awareness Month] It’s the fastest-growing neurological condition in the world Martin had deep brain stimulation (DBS) surgery; you’re actually awake for part of it Sleep can be an issue for people with Parkinson’s He never makes me feel like it’s a problem Tinkler and Ostrowski: “I liked spending time with her … And it seemed as if everything I liked she liked,” says Ostrowski.Credit: Dominic Lorrimer We were on a Parkinson’s panel – I’d been diagnosed in 2016 she in 2021 – and someone in the audience asked her a question Her eyes caught mine and something in me changed: I knew I’d found a kindred spirit About 10 to 20 per cent of people who have Parkinson’s are under 50 I was struck by how bright and bubbly she is We were talking about the upside of having Parkinson’s and there are advantages if you know where to look Probably the main thing is you get to reassess the way you’ve structured your life and what’s important to you You realise how much time you’ve wasted on things that don’t matter ‘I hadn’t really thought that I’d have an intimate future with anyone; my motor functions had gotten quite bad.’ Emma sent me a link to a podcast she’d been on talking about the disease It was pretty revealing: she spoke about her past and some of the things she was worried about in the future like whether she’d be able to be there for her two daughters I felt sad – daughters need their mum – but I also wanted to be a support to her I liked spending time with her; we’ve both had to retire so we were free during the day I brought her a croissant from my local bakery and she brought me one from hers It took a few weeks before I felt a romantic connection; I hadn’t really thought that I’d have an intimate future with anyone because I’d gotten quite bad with my motor functions I’d become almost rigid and be unable to speak or move which really restricted my capacity to leave the house I was only having four to six good hours a day thanks to the deep brain stimulation surgery We’ve had moments where she gets “stuck” – freezing of gait is a common symptom; it feels as if your feet are stuck in cement and you can’t move We’ll be on a train and have to miss the station Or she’ll grab my arm and tell me what pace to walk at whereas Emma’s used to organising her girls; she goes into parenting mode It’s important to me to preserve my dignity it doesn’t feel as if we have Parkinson’s; we don’t forget but I don’t now because my symptoms have stabilised and I’m confident the medical technology is going to keep up with the progression of the disease I’m fairly sure that I’ve got another 10 to 20 years twoofus@goodweekend.com.au To read more from Good Weekend magazine, visit our page at The Sydney Morning Herald, The Age and Brisbane Times have early-onset Parkinson\\u2019s disease Emma: I\\u2019d known Martin for a week when I asked him to come to a neurology appointment with me in May last year It\\u2019s always good to have another pair of ears when you see a specialist \\u201CThat\\u2019s talking dirty.\\u201D Silence I\\u2019ve gone too far too early.\\u201D Then he texted back 50 shades of caramelisation.\\u201D It was on He made us a shared Spotify playlist and said \\u201CI love you\\u201D after two weeks We\\u2019d both had a really shitty time with our disease before we met and now appreciate good times No couple ever knows what\\u2019s around the corner but having Parkinson\\u2019s brings up a lot of what-ifs People with late-stage Parkinson\\u2019s have a higher chance of developing dementia and I was picturing two old If my gait is slow or it feels as if my body\\u2019s tightening from the inside and I don\\u2019t have the bandwidth for a proper conversation while I\\u2019m dealing with symptoms I was having a bad time on New Year\\u2019s Eve We were leaving in 15 minutes to go to a party when I told him I didn\\u2019t think I\\u2019d be able to get there because my meds weren\\u2019t kicking in and I felt as if I had weights on my wrists and ankles \\u201CAre your legs working better than mine Can you grab my phone?\\u201D Or when he\\u2019s having difficulty putting his socks on \\u2013 one of the symptoms is a loss of dexterity in your fingers \\u2013 I help him He found it difficult to receive help at first because he\\u2019s been so independent we\\u2019re trying to raise awareness of how many younger people get Parkinson\\u2019s [April is ] It\\u2019s the fastest-growing neurological condition in the world Martin had deep brain stimulation (DBS) surgery; you\\u2019re actually awake for part of it \\u201CYou\\u2019ll know when you\\u2019re ready.\\u201D Sleep can be an issue for people with Parkinson\\u2019s He never makes me feel like it\\u2019s a problem We were on a Parkinson\\u2019s panel \\u2013 I\\u2019d been diagnosed in 2016 she in 2021 \\u2013 and someone in the audience asked her a question Her eyes caught mine and something in me changed: I knew I\\u2019d found a kindred spirit About 10 to 20 per cent of people who have Parkinson\\u2019s are under 50 We were talking about the upside of having Parkinson\\u2019s Probably the main thing is you get to reassess the way you\\u2019ve structured your life and what\\u2019s important to you You realise how much time you\\u2019ve wasted on things that don\\u2019t matter Emma sent me a link to a podcast she\\u2019d been on talking about the disease like whether she\\u2019d be able to be there for her two daughters I felt sad \\u2013 daughters need their mum \\u2013 but I also wanted to be a support to her I liked spending time with her; we\\u2019ve both had to retire so we were free during the day It took a few weeks before I felt a romantic connection; I hadn\\u2019t really thought that I\\u2019d have an intimate future with anyone because I\\u2019d gotten quite bad with my motor functions I\\u2019d become almost rigid and be unable to speak or move We\\u2019ve had moments where she gets \\u201Cstuck\\u201D \\u2013 freezing of gait is a common symptom; it feels as if your feet are stuck in cement and you can\\u2019t move We\\u2019ll be on a train and have to miss the station Or she\\u2019ll grab my arm and tell me what pace to walk at I don\\u2019t like having things done for me whereas Emma\\u2019s used to organising her girls; she goes into parenting mode It\\u2019s important to me to preserve my dignity it doesn\\u2019t feel as if we have Parkinson\\u2019s; we don\\u2019t forget but I don\\u2019t now because my symptoms have stabilised and I\\u2019m confident the medical technology is going to keep up with the progression of the disease I\\u2019m fairly sure that I\\u2019ve got another 10 to 20 years \\u2018We never get the shits with each other about this stuff because we know how it feels.\\u2019 \\u2018I hadn\\u2019t really thought that I\\u2019d have an intimate future with anyone; my motor functions had gotten quite bad.\\u2019 A new discovery in blood immune cells has put researchers one step closer to identifying a blood biomarker that would allow doctors to personalise treatments for Parkinson’s disease In a multi-disciplinary effort, researchers from the WEHI Parkinson’s Disease Research Centre have discovered that changes in the abundance of blood immune cells could be a potential marker of Parkinson’s disease progression The research was part of a project that analysed data from over 500,000 people Parkinson’s disease is the fastest growing neurological disorder worldwide and second in prevalence to Alzheimer’s meaning it will continue to get worse over time and there is still no cure or drugs to slow or stop the progression of the disease The current best estimate is that more than 200,000 Australians live with Parkinson’s in Australia Those figures are forecasted to double in the next 15 years The exact number of people with Parkinson’s is not known as there is no clinical diagnostic test In a team effort spanning both the Bahlo and Dewson labs from the Parkinson’s Disease Research Centre as well as WEHI’s Human-based Research and Clinical Trials group and WEHI Research Computing, researchers led by Professor Melanie Bahlo and Dr Fei Wang discovered a new link between blood immune cells and Parkinson’s disease The finding brings the team a critical step closer to a blood test that could be used for diagnosing and monitoring the progression of the disease “The ultimate goal is to be able to screen for Parkinson’s disease in a similar way to the national screening program for bowel cancer so people can get access to medication sooner,” Prof Bahlo said Mitochondrial dysfunction has long been associated with Parkinson’s disease and a potential biomarker that has emerged for measuring mitochondrial health is counting the ‘mitochondrial DNA copy number’ suggests the link between mtDNA-CN and Parkinson’s disease may not stem from mitochondrial dysfunction Mitochondria are the sources of cellular energy and have their own DNA that is different to nuclear DNA each with multiple copies of mitochondrial DNA need lots of mitochondria whereas others need far fewer With mitochondrial dysfunction known to play a major role in Parkinson’s disease previous thinking was that the number of mitochondrial DNA copies in blood samples could be used as a biomarker Because it is virtually impossible to count the exact number of mitochondrial DNA copies the WEHI team developed a software algorithm to estimate the count from a DNA sequencing method using blood samples testing it initially on a dataset of over 10,000 participants They discovered that lower levels of mitochondrial DNA in the blood are not directly linked to an increased risk and severity of Parkinson’s disease This apparent connection vanished when the team considered the different types of cells present in the blood They instead found a stronger link with certain immune cells This suggests that the previously reported relationship between mtDNA–CN and Parkinson’s is linked by immune responses in blood White blood cells are related to blood immune and inflammation responses It is known that people with Parkinson’s disease show elevated levels of neuroinflammation the researchers replicated their study using the UK Biobank analysing data from nearly 500,000 participants making it the most extensive study of mtDNA-CN in Parkinson’s so far highlighting the reliability of their methodological framework The researchers have made the specialised software they developed for estimating mtDNA-CN, called mitoCN freely available for use by teams around the world to drive forward studies beyond Parkinson’s disease Fox Foundation announced a newly identified biomarker that relies on spinal fluid to test for the presence of alpha-synuclein Because the test requires an invasive spinal tap making it more likely to be used by clinicians,” said Dr Fei Wang Biomarkers are not just important for diagnosing Parkinson’s A blood biomarker also has the potential to be used to track disease progression so clinicians can adjust medications to help deliver a better quality of life as well as measuring drug effectiveness during a clinical trial The research was funded by the Felton Bequest philanthropic donation as well as grants from the Michael J Fox Foundation Shake It Up Foundation Australia and the NHMRC By using this website, you agree to our use of cookies in accordance with our Privacy Policy and Terms of use. Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne have solved a decades-long mystery that paves the way for development of new drugs to treat and potentially prevent Parkinson's Disease. In world-first research published in journal, Science, WEHI researchers have discovered what a never-before-seen protein linked to the neurological disease looks like, and how it's activated. L–R: Professor David Komander, Dr Nicholas Kirk, Dr Sylvie Callegari and Dr Alisa Glukhova.(Supplied) Published: 12h agoSun 4 May 2025 at 10:45pm Published: 13h agoSun 4 May 2025 at 10:30pm Published: 13h agoSun 4 May 2025 at 10:00pm Download the ABC listen app to text and call your favourite live radio My beloved Converse All Stars had always been part of my identity But when they became painful and impractical it transformed my relationship with clothes Style and comfort have always been of equal priority for me I got my first pair of Converse All Stars at the mall in Indiana in the 1980s They were teal and yellow – I would fold the lip of the hi-top over to show off the lemony interior I wore low-top leather Converse with my white dress I’ve walked across cities from Rome to Mumbai Chicago to Oslo – all while wearing Converse or Fly London boots – looking for vintage one-offs and secondhand gems a degenerative disease that resulted in symptoms including difficulty moving Dystonia is a common symptom for those of us with young onset Parkinson’s; it involves the involuntary and painful twisting of parts of the body or when I’m tired – and more so as the disease progresses – this drastically curtails my mobility and dexterity sometimes I stumble and nearly or actually fall Parkinson’s also began to transform my relationship with clothes I found that my beloved All Stars had become no good for walking possibly because the soles were flexible and light Fly boots were also treacherous: the wedge soles created a high-stakes perch from which my ankles would collapse My footwear shift began after a transatlantic flight shared his tip: Nike tactical boots have stiff soles and lace-up ankle support ‘Soon I wore nothing else’ … Kimberly Campanello Photograph: Courtesy of Kimberly CampanelloThe Flys and All Stars languished in my closet; I found it hard to accept that I would never wear them again that were no longer comfortable – but for so long those shoes had felt like “me” and they were a part of my identity I wasn’t willing to sacrifice A friend suggested selling pieces I no longer wore on Vinted I listed everything that now made movement difficult and received warm and grateful reviews from those who bought them turning to Vinted for my new obsessions: one-of-a-kind funky shirts to wear under longish jackets Layering helps regulate temperature fluctuations that arise due to Parkinson’s and the side-effects of my medication I didn’t touch my old shoes for almost a year – not until the time came to invest in a new pair of Nikes I saw how much my beloved boots could fetch and made a reluctant listing I watched them sit motionless in my real and virtual wardrobes until I received an offer on a grey pair It was the first pair I let go and I wrote a personal note to the buyer explaining why I would be sad to give them up The buyer was also a longtime All Stars-wearer; she had just worn through a much-loved pair in the same colour She sympathised with my reluctance to part with my favourite footwear and told me to keep well but I still seek out clothes and shoes that will go the distance I have gained a greater understanding of the things that trip us up as well as the power of kind words to move us An Interesting Detail by Kimberly Campanello is published by Bloomsbury (£10.99). To support the Guardian and Observer, order your copy at guardianbookshop.com. Delivery charges may apply. Play Duration: 8 minutes 48 seconds8m Brought to you by As Australia's second-most common neurological condition, Parkinson's affects people from all walks of life. It's symptoms manifest themselves in ways that can impact their ability to do their job. But as ABC Wimmera's Breakfast presenter, the biggest challenge for Rebekah Lowe, diagnosed at 46 years old, was how it affected her speech. In this personal piece, Rebekah investigates how Parkinson's affects communication skills, and the therapies and treatments available to help. Rebekah was diagnosed with Young Onset Parkinsons at 46-years-old. (ABC Wimmera: Rebekah Lowe ) Metrics details Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational cryopreserved off-the-shelf dopaminergic neuron progenitor cell product (bemdaneprocel) derived from human embryonic stem (hES) cells and grafted bilaterally into the putamen of patients with Parkinson’s disease Twelve patients were enrolled sequentially in two cohorts—a low-dose (0.9 million cells n = 7) cohort—and all of the participants received one year of immunosuppression The trial achieved its primary objectives of safety and tolerability one year after transplantation with no adverse events related to the cell product putaminal 18Fluoro-DOPA positron emission tomography uptake increased Secondary and exploratory clinical outcomes showed improvement or stability including improvement in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort These data demonstrate safety and support future definitive clinical studies While these therapies have an important role in symptom alleviation in the early stages their efficacy inevitably wanes due to ongoing attrition of dopaminergic neurons often accompanied by unwanted side effects such as dyskinesias By delivering new midbrain neurons to the striatum cell therapy aims to replace the degenerated dopaminergic projections and to achieve a sustained clinical improvement in motor symptoms The lessons learned from these studies suggest a potentially substantial clinical benefit for cell therapy in PD; however these studies also highlighted the need for a scalable cell source of midbrain DA neurons compatible with stringent quality-control assessments and lacking unwanted cellular contaminants an intense effort ensued across the globe to identify a renewable source of human midbrain DA neurons from pluripotent stem cells (such as hES cells or human induced pluripotent stem (iPS) cells) that is suitable for clinical use The same cryopreserved cell product tested here Patients were enrolled sequentially into a low-dose then a high-dose cohort The diagram indicates the timeline of immunosuppression monthly laboratory and clinical assessments Ongoing follow-up is anticipated for a minimum of 5 years the Unified Dyskinesia Rating Scale (UDysRS) the Non-Motor Symptom Scale (NMSS) and the patient-reported outcome on the basis of the PDQ-39 questionnaire All safety data from all of the participants were used to conduct the formal analysis of the primary end point at 1 year after transplantation Secondary and exploratory end points were also assessed at 1 year and 18 months after transplantation No tests of statistical significance were performed due to the small number of participants Cells were loaded into a modified cannula (Smart Flow and administered stereotactically during a single surgical session under general anaesthesia Cells were delivered into the post-commissural putamen bilaterally through a single burr hole on each side nine cell deposits were made in each putamen (three passes of the cannula; three deposits per pass) Surgery was performed using a frameless MRI-guided approach with intraoperative imaging at one site (New York) and a frame-based stereotactic approach at the other site (Toronto) The participants received basiliximab 20 mg intravenously intraoperatively and postoperatively on day 4; methylprednisolone 500 mg intravenously immediately before surgery then tapered to oral prednisone 5 mg daily and continued for 1 year; and tacrolimus taken orally beginning on the day after surgery (day 1) and then adjusted to a target trough blood level of 4 to 7 ng ml−1 for a period of 1 year All of the participants remain engaged in the clinical follow-up In addition to the two SAEs reported in the 12-month post-transplantation analysis an SAE of gastrointestinal haemorrhage requiring hospitalization was reported approximately 15 months after surgery 3 months after discontinuation of prednisone This was assessed as unrelated to the study procedures and was subsequently resolved Through 18 months after transplantation, there were 78 cumulative treatment-emergent adverse events (TEAEs), described in Extended Data Tables 1–5 Most were mild or moderate in severity except for one fall that was deemed to be unrelated to treatment MRI imaging by 18 months did not show evidence of tumours or changes in the putaminal volume there were no reports of adverse events or clinical indications of graft-induced dyskinesias (GIDs) to date with intraoperative delivery of the total number of all intended cell deposits in all of the participants Secondary end points: individual MDS-UPDRS Part III OFF scores in the low-dose (a) and high-dose (b) cohorts at the baseline and at different timepoints after transplantation Individual PD diary good ON time at the baseline and at different timepoints after transplantation in the low-dose (c) and high-dose (d) cohorts Bold lines are mean ± s.d.; exact values are given as mean (s.d.) beneath each data point Exploratory end points: individual scores on MDS-UPDRS Part III ON (e) MDS-UPDRS Part II (g) and UDysRS objective subscore (h) at the baseline and at different timepoints after transplantation in the low- and high-dose cohorts The baseline value (0 months) is defined as the last recorded value before surgery The double dagger symbol (‡) indicates the exception that for MDS-UPDRS Part III OFF at 18 months after transplantation The total possible score for the MDS-UPDRS Part III scale is 132 for the MDS-UPDRS Part II scale is 52 and for the UDysRS objective scale is 44 Good ON time is the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia Source data Images of the 18F-DOPA PET uptake signal at multiple sections through the striatum presented as the mean uptake of all patients (n = 12 at all timepoints except at 18 months Images of 18F-DOPA uptake were produced by dividing each original PET image by the occipital count and then subtracting 1 Formula: image of 18F-DOPA uptake = (PET image/occipital count − 1) Longer-term clinical and imaging follow-up is ongoing to monitor for the possibility of delayed onset GIDs or other adverse events Coupled with the stabilization or possible improvement in other secondary and exploratory motor the data suggest a promise for potential clinical benefit these data need to be interpreted cautiously in view of the open-label study design the expected fluctuations in PD symptoms and the possibility of placebo effects Longer-term and larger studies are required to more rigorously evaluate the safety and efficacy of this cell therapy for PD The clinical data also show a greater amplitude of changes in UPDRS motor scores and reduction in OFF times the precise kinetics of hES cell-derived midbrain DA neuron maturation in grafts and their relative disease vulnerability remains unclear which complicates the dose-finding process our findings should be interpreted carefully within the context of a small and unblinded safety and tolerability study that achieved its primary outcome and was not designed to evaluate efficacy based on clinical outcomes the possible improvement in PD symptoms at 18 months after transplantation may translate in future trials to an important finding There are currently several ES-cell- or iPS-cell-based grafting studies that are ongoing or close to initiation in the US highlighting considerable enthusiasm for cell therapy for PD These studies will probably differ in many aspects surgical strategies and other criteria; they will therefore provide valuable insights into future study design and the value of cell grafting in PD our data support moving towards larger definitive clinical studies which were differentiated from hES cells (WA09 at passage 33) was performed at the Cell Therapy and Cell Engineering Facility (CTCEF) at MSKCC WA09 cells were thawed and expanded on Geltrex coated flasks/dishes in Essential 8 basal medium with supplement for 10–14 days Cells were split by Dispase (Stem cell Technologies) every 3–5 days at a ratio usually between 1:4 and 1:6 single cells WA09 were washed and plated on Geltrex at 400,000 cells per cm2 in Neurobasal medium with N2 and B27 (without vitamin A) containing 2 mM l-glutamine 0.7 µM CHIR99021 and 500 ng ml−1 SHH with 10 µM Y-27632 The medium was replaced daily thereafter without adding Y-27632 LDN and SHH were withdrawn from the medium Neurobasal medium (with B27) with 2 mM L-glutamine 1 ng ml−1 TGFβ3 and 3 µM CHIR99021 was added cells were dissociated to single cells with Accutase for 30–40 min and replated on plates coated with poly-ornithine (15 µg ml−1 Trevigen) at 800,000 cells per cm2 using the same medium as on day 10 the medium was switched to include 10 µM DAPT and CHIR99021 was withdrawn Complete medium changes were performed daily until collection at day 16 MSK-DA01 cells were dissociated with Accutase for 30–40 min and filtered through a 40 µm cell strainer The cell pellets were resuspended at a cell density of 8 million cells per ml of STEM-CELLBANKER and placed in a controlled-rate freezer (Thermo Fisher Scientific) for cryopreservation Cryopreserved vials were stored in the secured GMP Facility freezer and monitored 24/7 by a Datatron system baseline and preoperative visits before surgery the participants underwent a postoperative evaluation on day 10 A battery of questionnaires and clinical rating scales were administered during site visits throughout the study with a total follow-up of 5 years after transplantation; the participants completed PD diaries at home before each visit and adverse events were assessed throughout the trial 18F-DOPA PET studies and analysis were performed at a single imaging site by investigators blinded to clinical and dose information The participants underwent three-dimensional PET imaging at the baseline and at 12 and 18 months after transplantation high-sensitivity PET tomograph (GE Discovery IQ-5 ring PET/CT Scanner General Electric Medical Systems; parameters: full-width-at-half-maximum = 5 mm Acquisition began approximately 80 to 100 min after a 5.0 mCi intravenous injection of 18F-DOPA The participants paused antiparkinsonian medication 12 h before scanning and were given 150 mg of carbidopa orally within 120 min before 18F-DOPA injection in accordance with FDA prescribing information 18F-FDOPA PET image reconstruction used the VUEPointHD ViP (VPHD) method a 3D iterative OSEM (ordered subset expectation maximization) algorithm with 4 iterations and 12 subsets after corrections for attenuation and scatter The image resolution was approximately 5 mm in all directions We created a priori group mean of striatal to occipital ratio (SOR-1) images computed for each timepoint, as well as a priori VOI-based analyses. The SOR-1 images (Fig. 3) were derived to provide an anatomical visualization of potential change in group mean18F-DOPA uptake signal over the striatum across the timepoints The VOI-based analyses were performed to provide group × time quantification of 18F-DOPA uptake signal within prespecified regions within the striatum (that is surgical target region of implanted cells; caudate MRI studies of the brain (1.5 Tesla and 3 Tesla) were performed using standardized acquisition protocols at screening all of the participants had a Hoehn–Yahr ON score of 2; 11 participants had a Hoehn–Yahr OFF score of 3 and one participant (low-dose cohort; Canada) had a score of 2 Inferential statistical testing was not performed due to the small number of participants Descriptive statistics (mean (standard deviation (s.d.)) or percentage (counts)) were tabulated by cohort The trial was conducted in accordance with the protocol and all applicable local government laws including policies with foundations in the World Medical Association Declaration of Helsinki the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use An institutional review board at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine reviewed and approved the clinical protocol (submitted with the Article) and the patient consent form All of the participants signed the informed consent 18-518 on 6/8/2021; WCM IRB no: 1810019690 on 14 January 2019) A data safety monitoring committee and the institutional review boards monitored trial progression and data handling The Tri-institutional Human Embryonic Stem Cell Research Oversight committee (ESCRO) at MSKCC and WCM approved the study and the consent on 11 October 2019 Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Diagnosis and treatment of Parkinson disease: a review The impact of nonmotor symptoms on health-related quality of life in 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in Parkinson’s disease patients Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson’s disease model Biphasic activation of WNT signaling facilitates the derivation of midbrain dopamine neurons from hESCs for translational use Morphometry of the human substantia nigra in ageing and Parkinson’s disease Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease Movement Disorder Society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): process Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: endorsed by the American College of Clinical Pharmacy and International Society for Heart and Lung Transplantation: an executive summary Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report and clinical checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group in Neuroscience and Biobehavioral Psychology 8–16 (Elsevier The clinically important difference on the unified Parkinson’s disease rating scale Dopamine cell implantation in Parkinson’s disease: long-term clinical and 18F-FDOPA PET outcomes Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease Personalized iPSC-derived dopamine progenitor cells for Parkinson’s disease A Bayesian model of shape and appearance for subcortical brain segmentation Simple ratio analysis of 18F-fluorodopa uptake in striatal subregions separates patients with early Parkinson disease from healthy controls Blinded positron emission tomography study of dopamine cell implantation for Parkinson’s disease Dyskinesia after fetal cell transplantation for parkinsonism: a PET study Download references the staff at the Cell Therapy and Cell Engineering Facility (Memorial Sloan Kettering Cancer Center) and the members of the Feinstein Institutes for Medical Research (Northwell Health) for their contributions to this research This study was sponsored by BlueRock Therapeutics The sponsor (BlueRock Therapeutics) collaborated with investigators on trial design and data collection The initial work to develop bemdaneprocel (MSK-DA01) was supported by NYSTEM grant C028503 and MSK Core Grant P30 CA008748 Morton and Gloria Shulman Movement Disorders Clinic Donald and Barbara Zucker School of Medicine at Hofstra/Northwell clinical trial design and manuscript writing served as principal investigator and neurologist on the trial performed transplantation surgery as investigators on the trial analysed the data and contributed to the PET screening of trial participants contributed to the preclinical data and to the study design was a neurologist investigator on the trial and contributed to the trial design All of the authors contributed to and approved the manuscript is a scientific advisor and receives research support from BlueRock Therapeutics Neurocrine and Neuroderm; and has also received clinical trial support from BlueRock Therapeutics UCB and National Institutes of Health (NIH) Boston Scientific and Insightec; and is a scientific officer of Functional Neuromodulation has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from AbbVie Paladin Labs and UCB; and has received research support from AbbVie support and/or speaker honoraria from Novo Nordisk study investigator and site principal investigator to acquire and/or analyse PET/SPECT and MRI brain images in multicentre clinical trials of stem cell and gene therapies for PD; and has received research support and paid travel from BlueRock Therapeutics and Aspen Neuroscience and paid consulting services from Novo Nordisk is a scientific advisor and receives research support from BlueRock Therapeutics and is a scientific co-founder of DaCapo Brainscience has received honoraria for consulting from Abbvie AskBio and Certara; stock options for scientific advisory board participation from Axent Biosciences; honoraria for scientific advisory board participation from Bayer Canary Health Technologies and ProJenX; honoraria for DSMB meetings from MeiraGTx; research support from BlueRock Therapeutics and Weston Brain Institute; and honoraria for presentations from the American Academy of Neurology The other authors declare no competing interests Diagram detailing the disposition of all participants The 12 participants who passed screening were enrolled sequentially into the low-dose cohort (N = 5) or high-dose cohort (N = 7) Representative axial T1-weighted and sagittal Flair MRI images obtained at baseline Transplanted cells were indiscernible; needle tracks exhibit gliosis as expected and are best seen in the lower panels Volume of interest (VOI)-based analysis of 18F-DOPA PET uptake signal in the anterior putamen (a) posterior putamen (b) and the caudate (c) at baseline for individual patients in the low and high dose cohorts Data is obtained via the VOI method as described in the Methods section N = 12 for all timepoints with 2 exceptions: one patient missed the 18-month timepoint scan and another patient had their 18-month timepoint scan performed at week 91 (at ~21 months) post grafting (data included) Bold lines in each panel represent the mean ± SD Source data Images of 18F-DOPA PET uptake signal at multiple sections through the striatum and 18 months in the low dose cohort (top) and high dose cohort (bottom) Images were produced by dividing each original PET image by occipital count and then subtracting 1 Download citation DOI: https://doi.org/10.1038/s41586-025-08845-y Metrics details In this phase I/II trial at Kyoto University Hospital seven patients (ages 50–69) received bilateral transplantation of dopaminergic progenitors derived from induced PS (iPS) cells Primary outcomes focused on safety and adverse events while secondary outcomes assessed motor symptom changes and dopamine production for 24 months Patients’ anti-parkinsonian medication doses were maintained unless therapeutic adjustments were required Magnetic resonance imaging showed no graft overgrowth Among six patients subjected to efficacy evaluation four showed improvements in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III OFF score and five showed improvements in the ON scores The average changes of all six patients were 9.5 (20.4%) and 4.3 points (35.7%) for the OFF and ON scores Hoehn–Yahr stages improved in four patients Fluorine-18-l-dihydroxyphenylalanine (18F-DOPA) influx rate constant (Ki) values in the putamen increased by 44.7% with higher increases in the high-dose group This trial (jRCT2090220384) demonstrated that allogeneic iPS-cell-derived dopaminergic progenitors survived produced dopamine and did not form tumours therefore suggesting safety and potential clinical benefits for Parkinson’s disease Parkinson’s disease (PD) is characterized by the loss of dopamine (DA) neurons in the substantia nigra leading to a motor syndrome characterized by bradykinesia Medical treatment effectively alleviates PD symptoms in the early stages but chronic use results in complications such as motor fluctuations and drug-induced dyskinesias cell therapies to replace lost DA neurons have been investigated as an alternative treatment we received approval from the Japanese government and the institutional review board of Kyoto University Here we report the results of our clinical trial launched in 2018 Patients were recruited and evaluated at Kyoto University Hospital between August 2018 and January 2019 The first three patients were categorized into the low-dose subgroup while the remaining four were classified into the high-dose subgroup One registered patient was excluded before surgery owing to a COVID-19 infection The first patient received unilateral surgeries with an eight-month interval between procedures and was included only in the safety assessment Efficacy analysis was conducted on the remaining six patients the patients were enrolled in this clinical trial and underwent neurological evaluation for more than 6 months If no notable symptomatic changes were observed during this period patients were re-enrolled for surgery and underwent further neurological evaluation (including MDS-UPDRS) and an 18F-DOPA PET study brain imaging (MRI and PET) and neurological assessments (including MDS-UPDRS) were performed at 3 PET studies included 18F-DOPA (to assess DA synthesis) 18F-GE180 (to detect inflammation) and 18F-FLT (to assess cell proliferation) tacrolimus (0.06 mg per kg twice daily) was administered with the dosage adjusted to maintain target trough levels of 5–10 ng ml−1 The dose was reduced by half at 12 months and discontinued at 15 months Tacrolimus (0.06 mg per kg twice daily) was administered and adjusted to target trough levels (5–10 ng ml−1) with the dosage reduced by half at 12 months and discontinued at 15 months differentiated into tyrosine hydroxylase-positive (TH+) DA neurons improving the rotational behaviour of PD model rats and Ki-67+ (a maker for proliferating cells) cells were less than 1.0% and sparsely distributed in the grafts no 5-hydroxytryptamine (5-HT)-positive cells (a marker for serotonergic neurons) were detected No serious adverse events necessitating hospitalization or resulting in death were reported. All 7 patients (100%) experienced a total of 73 adverse events, comprising 72 mild events and one moderate case of dyskinesia (Supplementary Table 2) The most frequent adverse event was application site pruritus There were no apparent differences in the spectrum frequency and severity of treatment-related adverse events between the low-dose and high-dose groups and most were unlikely related to either cell transplantation or tacrolimus The single adverse event possibly related to cell transplantation was neck stiffness and painful dystonia in the right upper limb during the drug-on state Tacrolimus administration was well tolerated but potentially associated with adverse events in three patients (42.9%) increased gamma-glutamyltransferase levels (n = 1) nail dermatophytosis (n = 1) and renal impairment (n = 2) indicative of apparent inflammation in the putamen and surrounding areas Chronological changes in the UDysRS scores for each patient from registration (0 months) to the end of the observation period (24 months) for safety assessment with the mean represented by the black line Absolute and relative (percentage) changes at 24 months are shown on the right Chronological changes in MDS-UPDRS part III scores during the medication-off (c,d) and medication-on (e,f) periods for each patient from registration (0 months) to the end of observation (24 months) for efficacy assessment The absolute and relative (percentage) changes at 24 months are shown on the right Source data Chronological changes in 18F-DOPA Ki values (average of both sides) in the putamen for each patient from registration (0 months) to the end of the observation period (24 months) The Ki value changes from the baseline; the mean is represented by the black line The 18F-DOPA Ki value (average of both sides) changes from the baseline in the caudate nucleus for each patient indicating pathological deterioration in PD The ratio of Ki values between the putamen and the caudate nucleus highlighting the impact of cell transplantation on pathological deterioration The percentage changes at 24 months are shown on the right Semiquantitative 18F-DOPA images generated at 80–90 min after injection by subtracting the occipital background signal and normalizing the result to the occipital activity in patient PD08 The colour change from dark green to red in the bilateral putamen indicates increased 18F-DOPA uptake Source data Although PS cells are expected to be an alternative donor cell source to hfVM the safety and efficacy of iPS-cell-derived DA progenitors remains unclear This first clinical trial using iPS cells confirmed that iPS-cell-derived DA progenitors can survive without forming tumours and produce DA in the putamen of patients with PD there were no serious adverse events or GIDs Four out of six patients showed improvement in MDS-UPDRS part III OFF at 24 months after transplantation suggesting that grafted cells functioned as DA neurons While such effects may also apply to our trial further confirmation through long-term follow-up and post-mortem histological examinations is necessary The spectrum of adverse events was similar to those encountered with chronic DA replacement medication tacrolimus administration and brain surgery Neck stiffness and painful dystonia in the right upper limb were noted in PD01 during the drug-on state a phenomenon possibly related to the grafts Tacrolimus- and surgery-related adverse events were manageable and reversible we purified CORIN+ medial plate cells and eliminated lateral plate cells we detected no 5-HT+ cells in donor-cell-derived grafts in rat PD models This purification process may have contributed to the absence of GIDs in our trial our positron-emission tomography (PET) study at 3 6 and 12 months showed no 18F-GE180 uptake suggesting the absence of severe inflammation we discontinued tacrolimus treatment at 15 months no inflammation due to immune response was observed in the putamen and surrounding areas as evident by the absence of hyperintensity regions on T2-weighted and FLAIR MRI or increased 18F-GE180 uptake there was no clinical difference between HLA-matched and non-matched patients further confirmation through long-term follow-up and post-mortem histological examinations is necessary for definitive conclusions PD08) in this trial exhibited motor symptom improvements exceeding what could be attributed to placebo responses potentially due to DA synthesized by the graft This interpretation should be further validated through post-mortem histological examinations in the future younger patients with less severe symptoms appear to be more suitable candidates for this treatment refining patient eligibility criteria may enhance the efficacy of this treatment discrepancies were noted between the MDS-UPDRS part III scores and the Hoehn–Yahr stage The Hoehn–Yahr stage emphasizes postural instability and mobility issues whereas the MDS-UPDRS part III offers a more comprehensive evaluation of major motor symptoms in PD improved postural stability and mobility may account for the greater improvement in the Hoehn–Yahr stage compared with changes observed in MDS-UPDRS part III scores of this study which may have contributed to symptom improvement there was no difference in adverse events between low- and high-dose groups and neither graft overgrowth nor GIDs were observed implanting more cells across a broader area may be necessary to achieve more substantial therapeutic effects The favourable safety profile observed in this trial provides an opportunity to explore whether a higher dose across a wider region can offer greater clinical efficacy Although our results did not fully align with age-related findings it is notable that the worst case (PD05) was the oldest patient These latter factors may partially explain the variable clinical responses observed in this trial susceptible to influence from the placebo effect and physician bias Future studies should consider a double-blind placebo-controlled design to minimize these biases small-sample trial should be confirmed in multi-centre large-sample trials with appropriate controls autologous transplantation using iPS cells may also be a promising option in which a single treatment with tacrolimus effectively suppressed immune response during xenotransplantation Histological examinations from previous fetal cell transplantation cases have shown that grafted DA neurons survived for 9 to 16 years even with immunosuppression discontinued 6 to 18 months after transplantation tacrolimus treatment was discontinued at 15 months and a single MCB vial was thawed to induce DA progenitors for each patient Human iPS cells were maintained with StemFit AK03N media (Ajinomoto) on iMatrix-coated (Matrixome) six-well culture dishes Aggregate spheres were fixed with 4% paraformaldehyde Immunostaining was performed after incubation with an antigen retrieval reagent (LSI Medience) and blocking with 0.3% Triton X-100 and 2% donkey serum for 1 h Fluorescence images were obtained by using confocal laser microscopes (Fluoview FV1200 The antibodies used are described in the ‘Animal experiments’ section below Clinical data were collected by using EDMS-Online (v.3.1 Safety and efficacy outcomes were summarized using mean values Statistical analyses of the clinical data were conducted using SAS software (v.9.4 Statistical analyses of animal experiments were performed using GraphPad Prism (v.10.3.1 Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article All relevant data from this trial are included in the Article and Supplementary Methods. Source data are provided with this paper Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation MDS clinical diagnostic criteria for Parkinson’s disease A more efficient method to generate integration-free human iPS cells A clinical-grade HLA haplobank of human induced pluripotent stem cells matching approximately 40% of the Japanese population Kinetic analysis of the translocator protein positron emission tomography ligand [(18)F]GE-180 in the human brain The unified dyskinesia rating scale: presentation and clinimetric profile Movement Disorder Society—sponsored revision of the Unified Parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results Systematic review of levodopa dose equivalency reporting in Parkinson’s disease Levodopa dose equivalency in Parkinson’s disease: updated systematic review and proposals Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease Dyskinesias following neural transplantation in Parkinson’s disease Focal striatal dopamine may potentiate dyskinesias in parkinsonian monkeys Graft-induced dyskinesias in Parkinson’s disease: what is it all about Graft-induced dyskinesias in Parkinson’s disease: High striatal serotonin/dopamine transporter ratio Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate MHC matching improves engraftment of iPSC-derived neurons in non-human primates Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease The placebo response in double-blind randomised trials evaluating regenerative therapies for Parkinson’s disease: a systematic review and meta-analysis Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease Exenatide and the treatment of patients with Parkinson’s disease Rate of clinical progression in Parkinson’s disease Delayed recovery of movement-related cortical function in Parkinson’s disease after striatal dopaminergic grafts Progression of monoaminergic dysfunction in Parkinson’s disease: a longitudinal 18F-dopa PET study Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study Rate of progression in Parkinson’s disease: a 6-[18F]fluoro-l-dopa PET study in Recent Developments in Parkinson’s Disease Vol Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data Imaging proliferation in vivo with [F-18]FLT and positron emission tomography Estimation of nuclear population from microtome sections Download references We thank all of the patients who participated in this trial; Y Togashi for brain imaging; members of the Efficacy and Safety Evaluation Committee Toda for their advice; doctors and coordinators at the Institute for Advancement of Clinical and Translational Science (iACT) Toyooka for supporting this clinical trial; the technical staff of J.T.’s laboratory Baba for cell manufacturing; PD project members of Sumitomo Pharma Karino for regulatory support and cell manufacturing; and K This study was supported by a grant from the Research Project for Practical Application of Regenerative Medicine of the Japan Agency for Medical Research and Development (AMED) (23bk0104126h0003) to J.T These authors contributed equally: Nobukatsu Sawamoto Kyoto University Graduate School of Medicine Center for iPS Cell Research and Application Department of Diagnostic Imaging and Nuclear Medicine Department of Biomedical Statistics and Bioinformatics and Takayuki Kikuchi wrote the first draft of the paper contributed to the acquisition of clinical data contributed to the generation of human iPS cells and DA progenitor cells contributed to immunosuppressive therapy management All of the authors contributed to the analysis or interpretation of data and performed critical revisions of the manuscript received a grant for collaborative research from Sumitomo Pharma received a research grant from Nihon Medi-Physics received a research grant from Siemens Healthcare Nature thanks David Devos, Hideyuki Okano and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available intermediate cells (before CORIN-positive cell sorting) iPSCs and intermediate cells each form a distinct cluster while final products are divided into two clusters Relative proportions of cell types in each cell sample determined by K-means clustering of sc-RT-qPCR data indicate the final product consists of approximately 60% DA progenitors and 40% DA neurons Batch #20022 was the donor cells used for PD04 Violin plots of gene expression patterns in clusters of iPSCs and final products show gene expression changes during DA differentiation Violin plots of gene expression patterns across different batches of final products indicate stable expression among batches Source data Immunofluorescence images of donor cells on day 30 (n = 7 independent experiments) NURR1 (a) is a nuclear receptor expressed in DA neurons while FOXA2 (b) is a transcription factor expressed in the floor plate The merged image (d) shows that donor cells consist mainly of DA progenitors and some DA neurons Summary of cell transplantation experiments and results Low- and high-dose cell injections were administered to examine differences in cell survival and behavioural improvement Methamphetamine-induced rotation behaviour in rats with grafts shows improvement at approximately 24 weeks *** p < 0.001 versus vehicle group by a two-way analysis of variance (ANOVA) with Tukey’s multiple comparisons test Adjusted p value = 0.033 (20 weeks) and 0.045 (24 weeks) a marker for DA neurons) in representative grafts at 32 weeks (n = 4 independent experiments) Magnified image of the graft shown in panel j Immunofluorescence image of the graft double-labelled for TH and HNA-positive cells indicating donor-derived DA neurons (n = 4 independent experiments) Percentage of KI67-positive cells relative to HNA-positive cells for each graft and 9 (batch 21047) biologically independent animals Immunofluorescence image of the graft stained for HNA (green) and KI67 (red) Magnified image of the graft shown in panel n with an arrowhead indicating an HNA/KI67 double-positive cell Immunofluorescence image of the graft stained for HNA (green) and 5-HT (red) Magnified image of the graft shown in panel p showing the absence of HNA/5-HT double-positive cells Immunofluorescence image of the host Raphe nucleus as a positive control for serotonergic neurons (5-HT red) DAPI staining is shown in blue (n = 4 independent experiments) Source data and sagittal images are displayed from top to bottom Blue and yellow regions indicate areas within 3 mm of cell injection sites Changes in graft volume as measured by T2-weighted MR images of each patient Hyperintense areas within the blue and yellow regions were calculated (R: right and L: left) Source data The Hoehn and Yahr scale was evaluated at 3 “ON” indicates measurements taken while the patient was on medication while “OFF” indicates measurements taken after the patient had been off medication for more than 12 h Source data Chronological changes in LEDD for each patient from registration (0 M) to the end of the observation period (24 M) Absolute and relative (percentage) changes at 24 months are shown on the right Source data a, Chronological changes in the fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) Ki values for each side of the putamen for each patient from registration (0 M) to the end of the observation period (24 M), as a supplement to Fig. 3 semiquantitative 18F-DOPA images generated at 80–90 min post-injection by subtracting the occipital background signal and normalizing the result to the occipital activity for each patient (Pre-Op: pre-operation reflecting dopamine synthesis by grafted cells Relationship between 18F-DOPA uptake and motor symptom improvement (i) Plots of pre- and post-transplant Ki values and MDS-UPDRS part III OFF scores for six (PD02-08) patients Healthy and initial symptom ranges are indicated based on previous studies where Ki values for healthy individuals range from 0.010 to 0.017 and initial Parkinsonian symptoms emerge with Ki values between 0.0045 and 0.0073 (j) Changes in Ki values and MDS-UPDRS part III OFF scores for each patient Source data Supplementary Methods and Supplementary Tables 1–7 Detailed protocol for an investigator-initiated clinical trial of safety and efficacy of transplantation of human iPS-cell-derived dopaminergic progenitors for Parkinson’s disease Detailed plan for an investigator-initiated clinical trial of safety and efficacy of transplantation of human iPS-cell-derived dopaminergic progenitors for Parkinson’s disease Download citation DOI: https://doi.org/10.1038/s41586-025-08700-0 Researchers behind test using biomarkers say it could ‘revolutionise’ early diagnosis of disease Researchers have developed a simple and “cost-effective” blood test capable of detecting Parkinson’s disease long before symptoms emerge About 153,000 people live with Parkinson’s in the UK and scientists who undertook the research said the test could “revolutionise” an early diagnosis of Parkinson’s disease “paving the way for timely interventions and improved patient outcomes” Parkinson’s is a progressive neurological condition in which nerve cells in the brain are lost over time This leads to a reduction of the chemical dopamine which plays an important part in controlling movement analyses small pieces of genetic material known as transfer RNA fragments (tRFs) in the blood focusing on a repetitive RNA sequence that accumulates in Parkinson’s patients It also looks at a parallel decline in mitochondrial RNA which deteriorates as the disease progresses Mitochondria exist inside cells and generate energy By measuring the ratio between these biomarkers researchers said the test “offers a highly accurate providing hope for early interventions and treatments that could change the course of the disease” On a scale where a score of 1 indicates a perfect test while 0.5 shows the test is no better than flipping a coin The best clinical tests presently used on patients showing early signs of the disease scored 0.73, according to the study published in the journal Nature Aging. The test uses the same PCR technology used during the pandemic to confirm Covid cases. It works by amplifying the genetic material being targeted, which allows it to be detected. “This discovery represents a major advancement in our understanding of Parkinson’s disease and offers a simple, minimally invasive blood test as a tool for early diagnosis,” said Prof Hermona Soreq of the Hebrew University of Jerusalem, who supervised the study. “By focusing on tRFs, we’ve opened a new window into the molecular changes that occur in the earliest stages of the disease.” Prof David Dexter, director of research at Parkinson’s UK, said: “This research represents a new angle to explore in the search for a biological marker for Parkinson’s. In this case the marker can be identified and measured in the blood which makes it attractive for a future patient-friendly diagnostic test for Parkinson’s. “More work is needed to continue to test and validate this possible test, especially understanding how it can distinguish between other conditions that have similar early signs to Parkinson’s.” The study was led by PhD student Nimrod Madrer under the supervision of Prof Soreq at the Edmond and Lily Safra Center for Brain Sciences and the Alexander Silberman Institute of Life Sciences, at the Hebrew University, in collaboration with Dr Iddo Paldor from the Shaare Zedek Medical Center, and Dr Eyal Soreq from the University of Surrey and the Imperial College London. Connecting decision makers to a dynamic network of information, people and ideas, Bloomberg quickly and accurately delivers business and financial information, news and insight around the world ColumnistParkinson's Disease Finally Finds a Source of HopeNew studies are a step toward eventually using stem cell therapies to repair or protect the brain but important validation that stem cell treatments for Parkinson’s disease are viable They also are a step toward a future where stem cells can be used not just to treat but ideally to repair or prevent damage to the brain Getting there will take incredible coordination and a continued commitment to understanding the drivers of neurodegenerative diseases; we can’t fix what we don’t know is broken Keep in touch with NewYork-Presbyterian and subscribe to our newsletter While scientists have identified certain risk factors associated with Parkinson’s, the exact cause is unknown. “Every year Parkinson’s disease incidence is going up,” says Dr. Miran Salgado a neurologist at NewYork-Presbyterian Brooklyn Methodist Hospital “We know there is some connection to genetics and environmental toxins Parkinson’s disease causes nerve cells in the brain to deteriorate over time Some patients advance more rapidly than others “My take-home message is no two people with Parkinson’s progress at the same rate so don’t worry about the clinical stage so much and focus on the mental and physical functions,” says Dr “It’s also important to have hope because there are many tools we have now in our toolbox to make your life better and manage your symptoms over a long period.” who shared information on signs and symptoms of the condition Salgado: Parkinson’s disease affects the central nervous system and it is a constellation of many symptoms put together Movement problems are the core symptoms of the disease but we have since realized there are different manifestations and variations of Parkinson’s a revolutionary family practitioner in England wrote about six patients who had slowed motor movements a protein in the brain (called alpha-synuclein) becomes abnormal and infects the brain cells that produce dopamine Dopamine is a neurotransmitter that controls our motor system and that leads to the motor-related symptoms that we see in Parkinson’s disease Most cases of Parkinson’s are idiopathic, meaning that they occur with no known cause. Some cases seem to be genetic. The number of known genetic cases has gone up from approximately 5% about 20 years ago to say 10% to 15% now because we are finding more and more kinds of gene defects which give rise to this Parkinson’s disease Environmental factors may also play a role together with genetics We know that Parkinson’s disease is more common in rural areas where well water was used so it might be toxins like pesticides or insecticides getting into the drinking water There are also toxins people are exposed to in factories — solvents or fumigants — that have also been implicated as causing disruptions of nerve cells that give rise to Parkinson’s disease There is also new research suggesting that Parkinson’s may spread from the gut ascend to the brainstem and across the brain or the olfactory system The four cardinal features are related to movement and usually start on one side of the body: There are other manifestations that may appear earlier and before movement-related disorders They are important because they may help us detect the disease early and develop therapy to slow the progression Anyone can develop Parkinson’s disease, but studies show that the condition affects more men than women. Parkinson’s tends to affect people after age 60, but around 10% will have early-onset Parkinson’s (before age 50) cases earlier in life may be inherited or linked to gene alterations Diagnosing Parkinson’s disease consists of: Studies have also shown that a laboratory test called the alpha-synuclein seeding amplification assay was able to identify Parkinson’s in people with the disease as well as in those at high risk for developing it even if they were not yet showing symptoms The test requires the collection of spinal fluid or biopsies of the skin It can detect the protein alpha-synuclein with high accuracy which could help doctors begin treatment much earlier Unfortunately, we do not have therapies to slow the progression of Parkinson’s disease, and there is no cure. What we offer today is improving quality of life. There is a fair amount of evidence showing that moderate to high intensity exercises can help with managing the disease The medication commonly prescribed is called levodopa Nerve cells use levodopa to make dopamine to replenish the brain’s dwindling supply Other medications include dopamine agonists that work to stimulate the production of dopamine in the brain used to treat the involuntary movements seen later with Parkinson’s They increase the amount of dopamine by slowing down enzymes that breakdown dopamine in the brain There are surgical therapies like deep brain stimulation We do this when Parkinson’s is advanced to control symptoms which was approved by the Food and Drug Administration to treat Parkinson’s symptoms in 2021 Focused ultrasound uses ultrasound beams to make lesions in brain structures to control movements and improve function Gene therapy trials are about to begin at NewYork-Presbyterian under Dr. Michael Kaplitt. Monoclonal antibodies targeting alpha-synuclein are still being pursued. Also some diabetes drugs, such as GLP-1 antagonists have shown promise in slowing disease progression Miran Salgado, M.D., is a board-certified neurologist at NewYork-Presbyterian Brooklyn Methodist Hospital where he is a movement disorder specialist and chief of neurology He works with the Weill Cornell Medicine brain and spine team providing care for patients with Parkinson’s disease With a season ending injury at the start of 2024 there’s no doubt the last year has been tough for Melbourne Mavericks defender Lauren Parkinson (nee Moore) But there’s been one shining light throughout that time “I remember telling my teacher an excuse so I could leave the classroom and I ran to the other side of the school where Josh was to tell him I got my first contract.” Although the two have been together since high school the defender’s crush started when she was in primary school almost to the day they first started dating "It was probably one of the best things to happen to have a wedding to plan to keep me busy,” she said my training was very different to what I was used to the wedding was a nice distraction from the hard times “Planning a wedding was stressful but it was good fun the wedding was a tight-knit affair with 45 of the couple’s nearest and dearest and the couple created memories they will hold onto for life Reflecting back on the decision to join the Mavericks Parkinson recalled how Josh reacted to the news when he left I was going to be playing for the GIANTS and our life wasn't going to change at all,” she said “Then he came back and all of a sudden I was moving to Melbourne but he was super supportive of my decision.” Parkinson explained how the couple’s “unorthodox relationship” has made them strong over the years “We've been together but not stuck like glue and that's why we are where we are today,” she said “We left school and I moved to Sydney straight away for netball while he travelled up north to go to university then we had the hubs and we couldn't see each other very often then we lived together and now he still lives in NSW but comes and stays in Melbourne for a few months at a time “The fact we’ve spent quite a lot of time apart means I know who I am we've grown up together but apart at the same time I’m my own person and so is he and we do life together we will forget about all the time we spent apart Parkinson opened up on why she decided to leave NSW in the first place “I was at a point in my career where I wasn't feeling I was reaching my full potential and I was never out of my comfort zone,” she said “I was craving a bit of specialised defensive coaching; I wasn't quite getting that with the GIANTS as soon as I started speaking to her about the prospect of being a Mav I never really thought I'd see myself living in Melbourne it didn't really go to plan but I don't regret it." Parkinson having every netballers’ worst nightmare come to life her MCL and meniscus were also badly damaged I felt nothing was holding my leg together she had her whole family at the pre-season match in Sydney for immediate support "Josh came into the room when I got taken around the back and we were in all sorts for about 10 minutes,” she said it was really sad but at the same time special My brother and his wife and their newborn baby were there and it was the baby’s first netball game "It was nice to have them all there to distract me from the fact my season was done.” Alongside Parkinson every step of the way have been her teammates “I’m really lucky to be a teammate of Parmy (Amy Parmenter) “No one wants to have another person hurt themselves but Sasha having broken her leg a month or so before myself it was quite comforting to know I was never really alone in the situation the excitement and the opportunity of coming to a new club and being part of something completely fresh was stripped from us.” The rehab journey has been slow for Parkinson but she can finally see the light at the end of the tunnel my surgeon took quite a slow approach at the start to protect my meniscus,” she said which was really hard because as much as it was great being wrapped up by my friends and family I didn't get to be with the Mavs for the start of the season “I missed out on the first win and singing the song for the first time which was really hard but it was what I needed.. I felt my heart needed a little bit of time away because of how serious my injury was.” the rehab journey has been smooth sailing for the defender I've ticked off all the boxes as they've come along which I've been super grateful for,” she said “I'm back on court and contesting right now I feel like a netballer again for a long time I felt like a great walker "I don't want to say the hard part's over but I'm getting excited now because I can really see the light at the end of the tunnel.” Parkinson spends time as a support worker for What Ability a not-for profit charity bringing fun community experiences to the lives of people with disability The defender first started with the company after being inspired by some of her friends while she was in NSW I get to go and make someone's day by playing bowling with them or going to the beach “It’s amazing to see how the simplest things bring people joy.” Parkinson had a tough time finding her purpose "It was a bit of a struggle because I felt I wasn't Lauren the netballer “A lot of the work stuff you'll see on my Instagram is glamorous but I don't show the challenging times as much “But it's such a rewarding job no matter how hard a day might be it doesn't feel like work.” the 27-year-old is optimistic she’ll be back on the SSN court soon but it will be early in the first couple of weeks,” she said “I should be playing netball before then but we haven’t yet got an actual plan for a set date.” "I would love to come back bigger and better,” she said “A lot of us are off contract after this season and I want to be around for a couple more years I'd love to lock in another contract so I can come back I've gone without it for quite some time and I really want to show everyone who I am and want people to remember my name details how the retina in people with PD responds differently to light than it does in healthy people suggesting it could be used as an early biomarker of PD development As there is currently no single test for PD it is currently diagnosed clinically through a combination of observable symptoms the disease has been present for several years and the affected neurons are already engaged in an irreversible degenerative process That’s why it’s important to find biomarkers that detect Parkinson’s at an early stage of the disease,” said study leader Martin Lévesque professor at Université Laval’s Faculty of Medicine and researcher at the CERVO Brain Research Centre the researchers used electroretinography (ERG) a method that measures electrical activity in the retina in response to light to compare retinal function between individuals with early-stage Parkinson’s and healthy controls They found distinct differences in the b-wave which might indicate α-synuclein pathology occurring in outer retinal layers “The retina is a direct extension of the central nervous system and offers a noninvasive way of exploring the brain,” Lévesque said “An unusual response of the retina to light stimuli could be indicative of a pathology affecting the brain.” the team conducted both human and mouse model experiments Twenty patients diagnosed with Parkinson’s within the last five years underwent ERG tests using electrodes placed on the lower eyelid to record retinal responses to various light flashes Similar ERG tests were conducted in a transgenic mouse model that overexpresses the human A53T α-synuclein protein implicated in Parkinson’s pathology tested before any motor symptoms were evident “Our cohorts exhibited both sex-specific and general ERG anomalies with the most significant changes occurring in the b-wave which appear to reflect early disease stages,” the researchers wrote reductions in these waveforms suggest functional impairment of key retinal cells prior to overt neurodegeneration The study also noted stronger effects in female participants possibly due to sex-based differences in retinal physiology and disease progression This research builds on earlier studies that showed dopamine dysfunction in the retina may underlie visual abnormalities in Parkinson’s the current study is among the first to demonstrate specific ERG anomalies in early-stage PD patients and to link them to retinal alpha-synuclein pathology and dopamine-related dysfunction in animal models “The results we obtained for people with Parkinson’s had a distinct signature from those in the control group,” said Lévesque similar ERG differences were found even before the appearance of motor symptoms “This suggests that the functional manifestations of Parkinson’s could be detected at an early stage of the disease by retinal examination,” he added The implications for clinical care could be significant by which time substantial dopaminergic neuron loss has already occurred noninvasive ERG test could allow for earlier intervention “We could offer a functional retinal exam from the age of 50,” said Lévesque While the researchers showed that these observable changes of how the retina responds to light can determine early signs of PD the exact mechanisms of these changes are not yet known The investigators also noted that the specificity of the retinal signature needs to be confirmed with additional studies as well as comparative studies with other disorders such as Lewy body dementia the research provides a promising direction for future studies and the development of a retinal biomarker for PD this is the earliest recorded instance of ERG anomalies in diagnosed PD patients supporting the development of a diagnostic tool for early detection and monitoring with the potential to improve interventions and patient management,” the researchers wrote Next steps for the researchers include testing larger and more diverse cohorts and examining how retinal responses change with disease progression and treatment The team will also further investigate the mechanistic role of dopamine and alpha-synuclein in the retina Violent dreams could be an early warning sign of Parkinson’s disease and scientists are trialling a potential treatment Parkinson’s causes symptoms such as tremors in the hands More than 150,000 Australians are living with the disease which is most common in people over 60. and the rest may be associated with environmental factors such as exposure to pesticides or heavy metals. and men are twice as likely to be diagnosed as women. Other symptoms of prodromal Parkinson’s include loss of sense of smell difficulty distinguishing between different shades of the same colour A drug trial underway at Macquarie University is taking advantage of an early warning sign of Parkinson’s in the hope of stopping the disease before it causes permanent damage to patients’ brains. While Parkinson’s is not considered a fatal condition it seriously affects patients’ quality of life and increases the risk of life-threatening falls and infections. Research has identified that inflammation in the brain is a key driver of the disease before the debilitating motor symptoms begin to appear. That’s why research at Macquarie University is exciting global medical interest and raising hopes of possibly defeating the disease. In a partnership with Sydney biotech company Syntara Macquarie’s Professor of Cognitive Neurology is leading a world-first clinical trial of a drug originally intended as a treatment for fatty liver disease and eye disease but was found to be effective in reducing inflammation in rats’ brains. Professor Lewis hopes the drug will also successfully treat the neuroinflammation that drives Parkinson’s disease. Researchers say violent dreams could indicate signalling issues in the brain and be a warning sign of Parkinson’s. Professor Lewis is working with people aged between 50 and 80 who are regularly having violent dreams where they are punching Professor Lewis said it appears that damage to the brain’s neural pathways in the earliest stages of Parkinson’s disease causes inflammation in the brain The implications could be devastating. “If we can’t explain why somebody starts acting out their dreams after the age of 50 their chances of going on and get Parkinson’s disease or disease like Parkinson’s is 140 times greater than the average person in the population,” he said. Researchers have found that over a 12-year period, about 75% of people with isolated REM sleep behaviour disorder go on to develop either Parkinson’s or a related condition. The drug trail aims to see whether a pill can combat the inflammation which is a key driver of early disease. “We want to identify a pathway to a cure so we’re using a short exposure to a drug that we think will reduce the neuroinflammation,” Professor Lewis said. Once the motor symptoms of Parkinson’s appear there has already been substantial loss of more than 50% of the brain’s dopamine-producing cells. The researchers want to “cure” these conditions before people start losing those brain cells. Both his grandfather and half-brother had Parkinson’s but at the time he did not realise the disease might be hereditary. The first indication that something was changing was a shift in his dreams about three years ago. “I was living out my dreams for the first time and it was almost like the script to a movie. because I was thrashing around in bed and waking her up It might happen once or twice a week and then not again for months.” Mr Clowes was diagnosed with REM sleep behaviour disorder. After learning this could be an early sign of Parkinson’s Related reading: 9News, Brisbane Times Discover how we campaign for change on your behalf Learn more Copyright © 2025 National Seniors Australia. Website by bigfish.tv. National Seniors Australia acknowledges Traditional Owners of Country throughout Australia and recognises the continuing connection to lands, waters and communities. We pay our respects to Elders both past and present. Phil Parkinson made over 360 appearances as a player for Reading Wrexham manager Phil Parkinson admits the club have "a lot of thinking to do" as they face major decisions on their squad following promotion to the Championship And he says further discussions are needed on plans to shape the side as they prepare to begin summer recruitment Parkinson's side wrapped-up a historic League One promotion campaign with a 2-0 win at Lincoln City on Saturday. Celebrations will continue – with a fan event planned for Sunday at the Stok Cae Ras and players set to jet off for a party in Las Vegas – but Parkinson is aware that the club can waste little time in preparing for their first campaign at second-tier level in 43 years Wrexham will be restricted to a 25-man squad next term – including goalkeepers – which limits wriggle room on players with the club accepting they will need to make signings to cope with a third move up a division in as many seasons "We've got a lot of thinking to do," he said "We had a brief chat last night with (chief executive) Mike Williamson (director) Humphrey Ker and (director) Shaun Harvey "But it was brief and in the next couple of days we will have to sit down again and go through numbers and look what we have got to do to make us strong and competitive next season the key is to look at the numbers; the 25 is more than League One but includes keepers so we'll navigate our way around that." Parkinson has only a handful of players out of contract this summer including 38-year-old striker Steven Fletcher who could yet be handed extended terms after eight goals helped towards promotion The former Bolton boss said he did not want to discuss contracts before the end of the celebrations He has nine strikers on the books at present, including Paul Mullin and Ollie Palmer who have had opportunities severely limited in recent weeks, although he said on Friday he expected the "legends" to be back in pre-season. Parkinson did accept the numbers in the squad will have to be looked at ahead of the summer recruitment with the club's automatic promotion allowing extra time to make key calls "We will try and keep the players we've got recruit the best players we can within our budget and we will see towards the end of pre-season whether we've pieced together the squad we believe will be competitive," he said "It's hard to say that now because let's assess the market and have a look but it's so exciting the grounds our supporters will have so many great days "Players could go - I don't want to speak about it just after the last game – but when you go up automatically you have time to review everything "We've got a nice bit of time and it's about making the right decisions and we've done that pretty well over the last few years and the job now is can we do it again." Share on FacebookShare on X (formerly Twitter)Share on PinterestShare on LinkedInCINCINNATI (WXIX) -Twenty-three-year-old Sean Ryan won the Flying Pig Marathon in the men’s division while Tori Parkinson completed the women’s race The 26.2-mile run started near Paycor Stadium at 6:30 a.m. and wrapped around the city won first place in the men’s race with a time of 2:22:41 “(The Flying Pig) is a reminder of why I love running,” said Parkinson ‘I love this,’ this is why I love running.” Below is the list of the top three winners in the marathon and the Paycor half marathon: See a spelling or grammar error in our story? Please include the title when you click here to report it Study shows STING has dual function in neurodegenerative diseases The STING protein, which has been linked to cell damage and brain inflammation — two known contributing factors to Parkinson’s disease and other neurodegenerative diseases — has a dual function The researchers said their finding could have implications for treating Parkinson’s and other neurodegenerative diseases a process known as neuroinflammation that is known to be linked to these diseases Researchers at the University of Texas found that STING not only triggers inflammation but also helps repair lysosomes a discovery they said offers new insight into how the disease develops and potential ways to treat it “STING is well known as an innate immune signaling protein. This study uncovered a new nonimmune function of STING,” Nan Yan, PhD, professor and vice chair of Immunology at the UT Southwestern Medical Center, and lead author of the study, said in a university news story The study, “STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders,” was published in Molecular Cell Parkinson’s disease is caused by the progressive loss of dopaminergic neurons, the nerve cells that produce dopamine, a chemical messenger involved in the regulation of motor function. This results in a reduction of dopamine levels and the onset of Parkinson’s disease symptoms Studies have shown that lysosomal dysfunction impairs the degradation of stimulator of interferon genes (STING) This results in STING signaling activation that causes inflammation in the nervous system a driver of nerve damage in neurodegenerative conditions The team had previously shown that STING activation was associated with neuroinflammation in a lysosomal storage disease called Niemann-Pick disease type C1 inherited conditions that occur when lysosomes do not function properly the researchers used a mouse model of another lysosomal storage disorder Some of these mice also had the STING gene deleted Mice carrying only the disease-causing mutation showed significant increases in inflammation-related genes especially in brain immune cells called microglia and developed serious brain inflammation by the time they were about one month old Similar results were observed when researchers used mouse models of two other lysosomal storage diseases The researchers said these results indicate that STING is associated with neuroinflammation when lysosomes become damaged Mice with Krabbe disease also had increased levels of lysosome-related genes associated with lysosome repair and generation of new lysosomes in microglia an effect that was significantly reduced in mice without STING These findings were further confirmed when mouse- and human-derived healthy cells were treated with a chemical that activated STING and were demonstrated to be associated with a protein called transcription factor EB a protein that regulates the expression of certain lysosome-related genes STING-mediated TBEF activation was independent of the immune signaling function of STING it was tied to its role as a proton channel which allows it to move charged particles that lower pH inside lysosomes The researchers demonstrated that cells accumulate more damage when STING is lost indicating that the STING-TFEB pathway facilitates lysosomal repair after damage “We demonstrate that STING mediates both [disease-causing] neuroinflammation and beneficial lysosomal biogenesis in lysosomal storage disorder,” the researchers wrote “Genetic deletion of STING dampens neuroinflammation but also reduces lysosomal biogenesis thus eliminating both beneficial and pathological effects.” Developing a strategy to reduce STING’s role in inflammation while increasing its function in lysosome repair and generation could be a new therapeutic strategy for lysosome storage diseases Because lysosome dysfunction plays a relevant role in neurodegenerative diseases, including Parkinson’s, Alzheimer’s disease, and amyotrophic lateral sclerosis such a strategy could also be useful to treat these conditions This site is strictly a news and information website about the disease This content is not intended to be a substitute for professional medical advice Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition Never disregard professional medical advice or delay in seeking it because of something you have read on this website.