Research Shows Genetic Variants Are More Common in People with Parkinson’s Than Originally Thought
New Parkinson’s Foundation research has found that genetic variants associated with Parkinson’s disease (PD) are more common than researchers previously believed.
Investigators in the Parkinson’s Foundation PD GENEration: Mapping the Future of Parkinson’s Disease study found that 13% of participants have a genetic form of PD — a significant observation compared to long-standing estimates. Results from the first 3.5 years of the study, which examined a broad North American cohort, was published in the peer-reviewed scientific journal Brain.
PD GENEration reached its goal of 15,000 participants this spring, ahead of schedule. Through the study, the Parkinson’s Foundation offers genetic testing for PD-related genes to any person with a confirmed PD diagnosis.
PD GENEration is the first of its kind to return results via live genetic counseling in English or Spanish. This enables participants and physicians to make more informed decisions about their care, including enrollment in gene-specific clinical trials.
Key PD GENEration findings published in Brain include:
7.7% of participants carried a GBA1 genetic mutation, 2.1% of participants carried a PRKN genetic mutation, and 2.4% of participants carried a LRRK2 genetic mutation. All participants were informed about their genetic status through the genetic counseling component of the program.
The positivity rate for a genetic variant is significantly higher for individuals with high risk. Those with young-onset PD, high-risk ancestry (such as Ashkenazi Jewish, Spanish Basque, or North African Berber), or a first-degree relative affected with the disease had an 18% positivity rate. The positivity rate for individuals without one of those risk factors was nearly 10%.
Many of these participants may qualify for precision medicine trials, showing the feasibility and importance of broadly offering genetic testing.
“We did not anticipate the high positivity rate for genetic mutations, specifically the nearly 10% having a positive result even without any known genetic risk factors,” said Roy Alcalay, MD, MS, Tel Aviv Medical Center, Israel, and the Department of Neurology, Columbia University Irving Medical Center, and lead principal investigator for PD GENEration. “Further, the speed at which participants enrolled in PD GENEration is a testament to the interest of people with PD to obtain data on their genetic status. Taken together, the positivity rate and the high interest in getting genotyped will hopefully translate to increased participation in observational studies and clinical trials toward therapies targeting these genes, simplifying precision medicine clinical trials in PD.”
Announcing the Next Phase
PD GENEration is moving into its next phase with support from the Global Parkinson's Genetics Program (GP2), a program of the Aligning Science Across Parkinson's (ASAP) initiative. ASAP's funding allows the Parkinson’s Foundation to accelerate the study’s impact by focusing on those who have been historically underrepresented in research.
Through wide-scale recruitment, the study is reaching a larger and more diverse community in the U.S., Canada and Latin America. The Parkinson’s Foundation aims to enroll an additional 8,000 participants, including 2,400 in Latin America, during the next phase of the study.
“PD GENEration is designed to be inclusive and accessible to all populations, with the goal of improving clinical outcomes for everyone. We are proud that the data we have collected through PD GENEration reflects the largest and most diverse North American cohort ever tested – and even though we reached our initial recruitment goal of 15,000 this spring, bigger things are on the horizon,” said James Beck, PhD, Parkinson’s Foundation chief scientific officer.
Across the country and beyond, Parkinson’s Foundation volunteers are going out and making a difference in the lives of people with Parkinson’s disease (PD) and their loved ones. They help us spread awareness and resources to those who need it most.
The dedication from our volunteers is what makes the Parkinson’s Foundation what it is today. We are honored to recognize five exceptional volunteers at the national level, who each received a 2024 volunteer award.
Dr. Reversa Joseph - Great Lakes Chapter
Paul Oreffice Volunteer of the Year
“Volunteering for the Parkinson's Foundation is more than just a commitment; it’s a deeply personal mission. Each effort, whether it’s a presentation, a lecture, or a podcast, is a step towards improving the lives of those affected by Parkinson’s, honoring my father’s struggle, and ensuring that every patient receives the comprehensive, integrative care they deserve.”
“Along the way I have learned that there are many things, tips and tricks that the people who live the best with this disease share: exercise, positive thinking, being around others like themselves and giving back. The Parkinson’s Foundation is a great way to give back.”
As the somber saying goes, a parent should never have to bury their child. But in March 2023 Roland and Shelley Frankel had to do just that. Their son Graeme had been fighting Parkinson’s for five years and passed from an asthma-related emergency. To keep Graeme’s memory alive, the family decided to start a DIY fundraiser with the Parkinson’s Foundation.
“I really enjoy volunteering. I see it as another way to celebrate movement. I move my brain cells around; I motivate my soul to do good things; and volunteering moves forward the search for a cure.”
There are many powerful ways to get involved and support the Parkinson’s Foundation and our work to make life better for people with Parkinson's. Get started with our How You Can Help page. This page will give you options for volunteering, starting your own DIY Fundraiser, or even just donating to the cause.
You can also fill out a volunteer interest form to chat with our volunteer engagement team about how we can best put your skills to use. Help us bring life-saving information and resources to the hands of those who need them most.
Thanks to our wonderful donors and community, we are excited to announce that our Reach Further fundraising campaign exceeded its goal early. In just three years, we raised $38.4 million to accelerate progress in Parkinson’s disease (PD) research, improve care and increase access to quality-of-life programs.
“Exceeding our campaign goal is a huge milestone, and we are so grateful to every person who made this campaign a priority,” said John L. Lehr, president and CEO of the Parkinson’s Foundation. “These funds allow us to accelerate our mission and create lasting impact in the lives of people with Parkinson’s.”
Launched in 2021, the Reach Further campaign helped fund PD programs and provide resources to local communities across the nation, providing support to people with Parkinson’s and their loved ones.
Here are four of the ways your support of the Reach Further campaign helped us impact people with Parkinson’s:
1. Recruited more than 15,000 participants for PD GENEration: Mapping the Future of Parkinson’s disease, our landmark genetics initiative. We also expanded access to the study to Black and African American communities, as well as Spanish-speaking communities in the U.S. and throughout the Western Hemisphere.
Thanks to this expansion, more people with Parkinson’s know if they have a genetic form of PD and have received genetic counseling to understand their results. So far, the study has identified that 12.7% of participants have a genetic form of PD.
Increasing the number of people participating in PD GENEration, and ensuring we are testing a diverse population, an accelerate relevant clinical trials, bringing us closer to a better understanding of PD and identifying potential new treatments.
2. Launched Parkinson’s Virtual Biotech in partnership with Parkinson’s UK to build a pipeline of new drugs exclusively aimed to target Parkinson’s.
Taking a new drug from an idea to becoming an available medication can take years and upwards of one billion dollars. The Parkinson’s Virtual Biotech works to accelerate that timeline by building a pipeline of new drugs exclusively for Parkinson’s.
The Parkinson’s Virtual Biotech is directly investing in medications that either address symptoms or aim to slow, stop or prevent the disease altogether.
3. Expanded our Global Care Network, adding 18 new Center designations to provide better, more attainable care.
Finding the right care team can improve the health and quality of life of a person with Parkinson’s. Our Global Care Network aims to make high-quality care accessible to more people with Parkinson’s, while also providing health professionals the chance to advance their skills and share their knowledge.
Through expanding our Global Care Network, we are taking one step closer to our goal of ensuring all people with PD have access to the equitable and quality care they need, when and where they need it.
4. Awarded $4 million in community grants across the U.S., addressing critical needs such as exercise, mental health and care partner support.
From dance classes to Rock Steady Boxing workout classes, local PD programs empower people with Parkinson’s and help them find community support. Through our community grants, we are proud to support the dedicated professionals and volunteers offering vital programs and resources to people with Parkinson’s around the country. These programs foster local Parkinson’s communities and help people live better with PD.
THANK YOU for helping us make life better for people with Parkinson’s through your support of the Reach Further campaign. These impact-driven achievements could not have happened without your support. Your generosity continues to elevate our research, care and education programs to new heights.
Discover new ways you can help the Parkinson’s community. Learn more about the Parkinson’s Foundation at Parkinson.orgor 1.800.4PD.INFO (1-800-473-4636).
A Protein that Protects Against Brain Cell Degeneration Associated with Parkinson’s
Guanylyl cyclase C (GUCY2C) is protective against dopamine neuron degeneration, a hallmark of Parkinson’s, by helping the cell’s powerhouse.
A new study is the first to identify a brain receptor called GUCY2C as a potential way to fight dopamine loss.
Parkinson’s disease (PD) is caused by the death of neurons that produce dopamine — a feel-good chemical related to movement, mood and more — in the brain. Dopamine neurons are involved in movement and the loss of these neurons disrupts the brain's ability to regulate movement, leading to hallmark PD symptoms, such as tremors, rigidity and slowness.
One of the reasons that dopamine neurons die is due to dysfunction of mitochondria, the small oxygen-consuming and energy-producing powerhouses inside cells. Recent research has found a receptor on the surfaces of those Parkinson’s-associated dopamine neurons that may provide therapeutic ways to protect the mitochondria and prevent the progression of the disease.
The receptor, called guanylyl cyclase C (GUCY2C), was first discovered on the surfaces of cells in the intestine, but was recently found in a region of the brain called the substantia nigra pars compacta (SNpc). This area of the brain is affected in PD.
A new study led by Scott Waldman, MD, PhD, and funded by the Parkinson’s Foundation 2023 Impact Award, gives a clearer picture of how GUCY2C signaling can provide protection against mitochondrial dysregulation and dopamine neuron degeneration that leads to PD. According to the study, in people with Parkinson’s, dopamine neurons make extra GUCY2C receptors.
About the Study & Results
Dr. Waldman and his team studied mice with and without the GUCY2C receptor. They found that loss of GUCY2C led to mitochondrial dysfunction, oxidative stress and cell death within the part of the brain impacted by PD, suggesting a protective nature of GUCY2C.
When the researchers gave the two groups of mice a toxin that induces PD symptoms by targeting mitochondria in dopamine neurons, only mice that did not have GUCY2C receptors had higher rates of dopamine neuron death. In contrast, mice with GUCY2C increased their production of the protein upon treatment with the toxin, further indicating a protective role.
The researchers also found that cyclic GMP (cGMP), a byproduct of GUCY2C activation, protected dopamine neurons from oxidative stress. In neurons grown in a petri dish, adding a molecule that increases cGMP protected dopamine neurons from oxidative stress and mitochondrial dysfunction when they added the PD-inducing toxin.
These results indicate that in Parkinson’s disease, the increase in GUCY2C might be the body's attempt to protect dopamine neurons from damage. It may be possible to develop a molecule that targets GUCY2C or use existing drugs that increase cGMP to protect dopamine neurons from damage.
Highlights
Loss of the receptor GUCY2C led to dopamine neuron degeneration in mice — in other words, not having the GUCY2C receptor led to neuronal dysfunction in brain regions implicated in PD.
A molecule that increases cGMP (a byproduct of GUCY2C activation) protected neurons grown in a petri dish from mitochondrial dysfunction and cell death when the researchers added a toxin that induces neurodegeneration.
Because GUCY2C is increased in people with Parkinson’s, the study results suggest that the increase in GUCY2C may be the body's attempt to protect dopamine neurons from damage.
What does this mean?
This study is the first to identify the receptor GUCY2C as a possible defense mechanism against dopamine loss. This research marks the beginning of what can be a new way to significantly slow down the progression of Parkinson’s.
Since GUCY2C appears to protect dopamine neurons in the brain, researchers could explore the possibility of stimulating GUCY2C as a treatment for PD. They could also try increasing cGMP, a byproduct of GUCY2C activation. This could potentially prevent the degeneration of dopamine neurons, a hallmark of the disease.
The study also found that people with PD have high levels of GUCY2C, which may also serve as an early indicator of Parkinson’s.
What do these findings mean to the people with PD right now?
With more research, GUCY2C could be a potential biomarker doctors can use to detect PD earlier. Having access to early biomarkers are critical for early therapeutic interventions for people with PD.
In addition, GUCY2C is a promising therapeutic target to prevent or treat PD. While developing a treatment that targets GUCY2C or its byproducts could take time, it remains important for researchers to identify as many potential treatments as possible. People who are currently experiencing Parkinson’s symptoms should talk to a healthcare provider.
Learn More
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.
What can you expect as Parkinson’s disease (PD) progresses? What are the signs and symptoms of each stage? Although the loss of dopamine is universal for people with PD, each person experiences a unique combination of movement and non-movement symptoms and disease progression.
In our latest Neuro Talk, Chief Scientific Officer James Beck, PhD, discusses the different stages of Parkinson’s disease progression and strategies for living well.
Episode 169: Implications of Gene-Based Therapies for Parkinson’s Disease
Gene-based therapy for Parkinson’s disease is an area of research that is currently being developed. It works by introducing genetic material into the brain, which can then “instruct” cells to produce compounds that can potentially alleviate symptoms of Parkinson’s. Although years have gone by since the first gene-based clinical trial, there is still much to learn before fully realizing its potential impact to treat Parkinson’s disease.
In this episode, Movement Disorders Neurologist, Andrew Feigin, MD of New York University Langone Health discusses what gene-based therapy is, how it differs from cell-based therapy, different trials currently in progress, and considerations for future research.
Released: May 28, 2024
Dr. Andrew Feigin is a Movement Disorders neurologist and Professor of Neurology at NYU Langone Health, where he is the Director of the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders. He has been involved in clinical research for Parkinson’s disease and related disorders for more than 25 years, and he has been a site principal investigator on more than 30 National Institute of Health and industry-sponsored clinical trials of new treatments for Parkinson’s disease (PD) and Huntington’s disease (HD). In addition, Dr. Feigin has had leadership roles in several early phase clinical trials and advanced multicenter clinical trials. In addition to his research interests, Dr. Feigin has remained a committed and busy clinician caring for patients with PD and related movement disorders.
Meet a Researcher Working to Stop the Spread of Misfolded Proteins in the Brain
Parkinson’s disease (PD) progression occurs in part because of a misfolded protein called alpha-synuclein that spreads in the brain. Alpha-synuclein forms clumps that clog brain cells (including neurons), leading to their eventual deterioration. Over time, the clumping kills neurons and impairs the brain’s ability to produce dopamine, leading to Parkinson’s symptoms.
Sunil Kumar, PhD, a recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is working on a new way to stop this spread using foldamers, which mimic the chemical and structural fingerprints of clumping alpha-synuclein and prevent this toxic process.
Foldamers are bioengineered compounds designed to fold into specific shapes, similar to how proteins, like alpha synuclein, fold and behave in the body. Understanding how foldamers fold and their unique structures could lead to the development of new therapeutics.
Dr. Kumar explained that while there is other research being done to prevent alpha-synuclein clumping, his lab’s approach at the University of Denver is unique because they are using foldamer molecules. Many other approaches use either antibodies, which are effective, but large, and have difficulty crossing the blood-brain barrier, or small molecules that are not very specific and therefore not effective in targeting alpha-synuclein.
“We came up with this idea of foldamer molecules, which are as specific as antibodies but they are much smaller in size, allowing them to cross the blood-brain barrier efficiently, which is essential when making a drug for Parkinson’s,” said Dr. Kumar.
“With this foldamer strategy, our lab has identified two or three lead compounds that have advanced through the initial pre-clinical stages,” he said. “We have optimized their activity all the way up to mouse models and they have shown very nice activity to rescue all the Parkinson’s disease phenotypes. We are now in the second phase where we are optimizing their pharmaceutical properties.”
So far, his lab has seen success with this strategy, and he hopes it will lead to a new treatment for people with PD in the future.
“We are very hopeful that once we pass the current testing stage, we can move to the clinical phase and find a drug to stop the progression of the disease or slow it down,” Dr. Kumar said. “This would increase the lifespan of people with Parkinson’s disease, as well as their quality of life.”
Disease-Modifying Research Pipeline Holds Possibility for Parkinson’s
Though there is still a lot we don’t know about Parkinson’s disease (PD), therapies aimed at modifying disease progression are poised for major breakthroughs. Researchers are excited about the potential of current studies to improve, slow or someday stop PD.
This article is based on Research Update: Working to Halt PD, a Parkinson’s Foundation Expert Briefing webinar presented by Lorraine Kalia, MD, PhD, FRCPC, assistant professor in the Division of Neurology, Department of Medicine at the University of Toronto and scientist at Toronto Western Research Institute and Tanz Centre for Research in Neurodegenerative Disease.
Understanding PD Progression
Parkinson’s is not a static condition — it's an intricate, progressive disease that evolves over time. Uncovering its many complexities is one of the challenges PD researchers face as they work toward halting its progression.
As people age, the loss of some brain cells is expected. In Parkinson’s this loss happens at a much faster rate. Neurodegeneration, the progressive loss of neurons that produce dopamine — a feel-good chemical related to movement, mood and more — is tied to movement and non-movement symptoms that develop in PD. As time progresses, new symptoms may develop or worsen.
Right now, we have therapies that can treat Parkinson’s symptoms — lessening tremor, easing mobility, improving mood and more — but we can’t stop the disease. Research is at the beginning stages of discovering disease-modifying therapies that might slow or stop the loss of dopamine-producing neurons.
Exploring Disease-Modifying Therapies
Therapies that can potentially change the course of Parkinson’s are rapidly evolving. A 2023 analysis of 139 PD drug therapy clinical trials registered as active on the ClinicalTrials.gov website showed 76 were investigating symptomatic treatments and another 63 were exploring disease-modifying therapies.
Though these therapies are still on the horizon for use in PD, the first drug to change the course of multiple sclerosis (MS) — a condition that affects a person’s spinal cord and brain and spine — was discovered in 1993. Now, there are more than 20 disease-modifying therapies for MS. One reason medications to slow MS progression have been so successful is that scientists have a way to identify the disease and observe its response to therapies. This is known as a biomarker.
Researchers are beginning to discover possible biomarkers related to Parkinson's. PD is tied to the abnormal clumping of a protein called alpha-synuclein in the brain. Alpha-synuclein can act as a biomarker in PD. Reliable biomarkers can potentially lead to the ability to diagnose Parkinson’ sooner, track disease progression and help researchers design and test therapies that might change the course of the disease.
Changing the Course of PD
Neurodegeneration in Parkinson’s — progressive damage to normal, healthy brain cells — can cause cell dysfunction and death. This process may be reversible. Cell protection is an approach that seeks to slow or prevent this process.
Areas of research that focus on cell protection are expected to show the most progress in the near future. They include:
One of the most important PD symptom management tools, it improves heart, muscle and bone health, lung function, as well as cognitive and mental health. Exercise can also reduce the risk of fractures and falls. Research shows it can also help maintain movement in Parkinson’s, slow disease progression and improve symptoms; it may also provide cell protection.
Studies suggest exercise might reduce inflammationin PD and increase growth factors — proteins that stimulate cell growth and influence how a cell functions.
Alpha-synuclein
This protein is abundant in the brain. Though it’s unclear why, alpha-synuclein malfunctions in PD and the proteins start to misfold and stick together, forming increasing buildups. These ultimately form Lewy bodies.
Brain cells are complex and require several healthy components to function. Researchers think malformed alpha-synuclein can disrupt these cell functions and can impact nearby brain cells. Targeting misfolded alpha-synuclein may protect brain cells from dying. There are many potential ways to do this. Researchers are currently exploring prescription therapies that could:
Reduce alpha-synuclein production in the cell (Buntanetap ION464.)
Degrade corrupt alpha-synuclein (Minzasolmin.)
Reduce or prevent problematic alpha-synuclein moving from one cell to another (Prasinezumab ACI-7104.056 and UB-312.)
There is a connection between genetics and Parkinson’s. GBA is the most common Parkinson's-related gene, occurring in 5 to 10% of people with PD. Carriers may experience PD symptoms at an earlier age compared to those who do not have a genetic form of PD. LRRK2 is involved in about 5% of people with a family history of Parkinson’s. Carriers may have milder symptoms of dementia and depression.
Lysosome, one of the disposal systems of the cell, is an enzyme that breaks down and gets rid of waste. One thing it may get rid of is alpha-synuclein. GBA lives within the lysosome. In people with a GBA gene mutation, the lysosome enzyme may be underactive. Researchers are currently exploring prescription therapies that could enhance lysosome activity and make it work better.
In Parkinson’s, a LRRK2 mutation impacts the autophagy lysosomal pathway, another cell waste disposal system, causing overactivity. Slowing this activity might reduce neurodegeneration. BIIB094 and BIIB122, intended to curb this excess activity, are currently in clinical trial.
Repurposing Existing Drugs
Therapies already approved for other diseasesmay hold great potential in Parkinson’s. If proven effective, they can be fast-tracked to begin treating people with PD because they have already gone through clinical trials to demonstrate their safety.
More than one-third of the drugs in current PD clinical trials being tested as potential disease-modifying therapies are repurposed drugs.
Amantadine is an example of drug repurposing in Parkinson’s as it was originally developed as a flu treatment. In the 1960s, a woman with PD taking amantadine for the flu told her doctor her Parkinson’s symptoms felt much better. Subsequent clinical trials confirmed the benefits of amantadine on some PD symptoms. The medication was initially prescribed for movement symptoms, before levodopa became the most effective, widely available Parkinson’s drug. Today, amantadine is primarily used to treat dyskinesia.
Ambroxol is currently approved as a cough suppressant and is in clinical trial to enhance GBA activity. It has quickly moved from Phase II onto Phase III clinical trials.
GLP-1 receptor activators are another category of medications that may hold major disease-modifying potential, are currently making headlines. These drugs were primarily developed for diabetes (one of the most familiar brand names in the category is Ozempic).
GLP-1 receptor activators bind to a receptor on the outside of a cell, causing a chain of activities that can potentially improve memory, cell survival and effects of mitochondria, while reducing inflammation and alpha-synuclein. Exenatide is the first of these to be tested. Various versions of it, NLY01 (slow-release) and PT320 (pegylated), have been or are in clinical trials.
Two related medications, Liraglutide and Lixisenatide, have been or are also in clinical trials. The results of a phase II trial of Lixisenatide published in the April 3, 2024 New England Journal of Medicine are causing a lot of excitement. Lixisenatide therapy in participants with early PD resulted in less motor disability progression than placebo at 12 months. The study is poised to move on to a phase III trial.
Cell Replacement
Early studies to investigate whether brain cells could be replaced in Parkinson's isolated and removed dopamine-making stem cells from human fetal tissue and grafted them into the brains of research participants with PD. While the research showed promise, nuances and complications limited long-term research.
Remarkable advances in stem cell technology over the past decade have led to the ability to make dopamine-producing cells from a person’s blood or skin cells or from embryonic stem cells, unlocking a new generation of stem cell research. There are ongoing clinical trials in countries around the world, including the U.S., investigating potential benefits in Parkinson's.
Cautious Optimism
Parkinson's disease looks different for different people. Different causes may spur its development. Multifaceted research is essential to moving forward.
Science must keep an open mind, follow the evidence and — when disease-modifying treatments become available — target people with the right treatments at the most impactful stages of the disease.
Ultimately, Parkinson’s is a global disease with symptoms and a rate of progression that is unique to each person living with it. It is important to pursue different avenues of research because there may be more than a single cure.
Learn More
The Parkinson’s Foundation works improve care for people with PD and advance research toward a cure.
Discover how we are working to close gaps in knowledge about PD: Advancing Research
Explore ongoing Parkinson’s research studies: Join A Study
Learn about PD GENEration — a global genetics study that provides genetic testing and counseling at no cost for people with Parkinson’s.
A Skin Test Could Detect Parkinson’s and Related Diseases
New research indicates that a skin biopsy could possibly lead to accurate diagnosis of Parkinson’s and other neurodegenerative diseases.
Currently, there is no single test to diagnose Parkinson’s disease (PD). Doctors rely on symptoms, which can mean a delay in diagnosis as early symptoms can be hard to distinguish from other common ailments. A new study in the Journal of the American Medical Association (JAMA) shows that a skin biopsy test can reliably detect Parkinson’s and other related diseases.
Parkinson’s, along with dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF) are four diseases characterized by progressive neurodegeneration and disability. Together this group of diseases are called synucleinopathies because the nerve cells accumulate an abnormal version of the protein alpha-synuclein, which is also referred to as phosphorylated alpha-synuclein (P-SYN).
Previous research indicated that P-SYN could also be found in nerve cells present in the skin. The new JAMA study shows that small amounts of skin taken from the leg, thigh and back of the neck can be analyzed to detect P-SYN in people who have synucleinopathies.
A similar study published last year detected alpha-synuclein in a slightly different test referred to as a seed amplification assay (SAA) analysis . In that study, investigators collected spinal fluid from people with early Parkinson’s. A skin biopsy is considerably less invasive than a lumbar puncture (also known as a spinal tap), which is why this study has generated a lot of interest.
About the Study & Results
The study enrolled 428 participants; 277 were diagnosed with Parkinson’s or another synucleinopathy (DLB, MSA or PAF), along with 151 people who had no history of neurodegenerative disease. Each participant had three skin biopsies that were analyzed in the laboratory.
Of those confirmed to have a synucleinopathy, the biopsies tested positive for P-SYN 92.7% of the time with Parkinson’s, 98.2% with MSA, 96% with DLB, and 100% with PAF. For people who did not have a diagnosis, only 3.3% of the biopsies tested positive for P-SYN.
The researchers also found a correlation between the amount of P-SYN in the biopsies and the severity of the participants’ symptoms.
Biopsy detection of P-SYN was the lowest among those with Parkinson’s (at the rate of 92.7% positive), potentially because there are different subtypes of Parkinson’s or because some genetic causes of Parkinson’s, there may be less P-SYN accumulation. However, study results did not address genetic variations associated with the diagnosis of PD.
However, it’s possible that skin biopsies could detect many cases of Parkinson’s before hallmark symptoms appear — such as tremor and trouble walking. Researchers suspect that P-SYN begins to accumulate in the nerve cells before there are noticeable changes to a person's movement. More research will be needed to confirm this suspicion.
The authors of the study speculated that the 3.3% of the biopsies that tested positive for P-SYN among those who did not have a neurodegenerative disease diagnosis, may indicate the potential for a future synucleinopathy diagnosis. However, longer-term follow-up is needed for confirmation.
More research is needed to determine when P-SYN can be detected in the progression of these diseases, and in those who don’t have symptoms, whether P-SYN detection is always predictive of future disease.
Highlights
The study looked for a skin biopsy marker of Parkinson’s and other related neurodegenerative diseases, called phosphorylated alpha-synuclein (P-SYN).
Among those confirmed to have Parkinson’s, 92.7% of the skin biopsies tested positive for P-SYN.
Among those who did not have a neurodegenerative diagnosis, only 3.3% of the skin biopsies were positive for P-SYN.
The amount of P-SYN in the biopsies correlated with the severity of the participants’ symptoms.
What does this mean?
This skin test method could be used to detect Parkinson’s and related diseases before symptoms appear. By identifying the disease before symptoms manifest there is a possibility of developing treatments before the condition progresses. With a reliable way to identify these diseases at their earliest stages, researchers could more effectively evaluate potential treatments and hopefully bring them to people living with PD sooner.
Additionally, because the researchers found a correlation between the amount of P-SYN in the biopsies and the severity of symptoms, the test might be used to test whether potential treatments are working. For example, if a drug treatment reduces P-SYN, it could indicate that the treatment is having an effect.
More research is needed before a skin biopsy would be considered useful for someone who does not have symptoms, as we don’t yet know how early the test could detect whether they will likely have Parkinson’s or other related diseases. We also do not know if some people could have P-SYN in their skin, but never develop symptoms.
What do these findings mean to the people with PD right now?
The skin biopsy test is commercially available today. It is called the Syn-One Test® and doctors may use it to confirm a synucleinopathy, which may lead to a Parkinson’s diagnosis. A doctor assesses test results alongside other in-office tests and present symptoms to confirm a Parkinson’s diagnosis. If you are already diagnosed with Parkinson’s disease and respond to levodopa treatment, the skin biopsy will likely not add anything to your current management and would not be necessary.
According to the Syn-One Test® manufacturer, Medicare typically covers 80% of the total fee. Insurance may cover all or some of the test fee.
When diagnosing possible Parkinsonism, instead of the Syn-One Test, a doctor may order a DaT scan. Similarly, a DaT scan does not differentiate between the various forms of parkinsonism. Usually if a doctor orders a test to help confirm a Parkinson’s diagnosis, the test is either the skin biopsy test or a DaT scan — not both.
Talk to your Parkinson’s doctor about the Syn-One Test®. If you have already been diagnosed with Parkinson’s and you are responding to therapy, your doctor will most likely not recommend the test. If you are in the process of being diagnosed or confirming a diagnosis, a neurologist or a neurologist with specialty training in movement disorders if available in your region, may consider this test to confirm a diagnosis of a synucleinopathy. Remember that this test is relatively new, so not all Parkinson’s doctors are utilizing it.
Learn More
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.
The Parkinson’s Foundation drives a multi-disciplinary research strategy to close the gaps in knowledge about Parkinson’s – from its basic biology to its impact on the brain and its effects on people. We work to accelerate our findings, quickly applying them to improved treatments and care today.
We spur discovery by taking a comprehensive, big-picture approach to research. This approach is vital to identifying the fastest lanes to new therapies for the 10 million people living with Parkinson's in the world.
