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.

Enroll Now

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.

Discover the drugs in development right now

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.

Find expert care near you

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.

Find a program in your community

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.org or 1.800.4PD.INFO (1-800-473-4636).

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.

• My PD Story: Scott Waldman, MD, PhD – learn more about this study and Dr. Waldman
• Neuro Talk: PD Progression
• Getting Diagnosed

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.

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.”

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.

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:

Exercise

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 inflammation in 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.)

GBA1 and LRRK2 Genes

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 diseases may 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.

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.

• Getting Diagnosed
• Neuro Talk: Why Are More People Getting Diagnosed with Parkinson’s?
• Detecting Early Parkinson’s with a Wearable Movement-Tracking Device

A clinical trial shows that an ultrasound treatment can help with involuntary and impaired movement for people with Parkinson’s.

People with Parkinson’s disease (PD) experienced significant improvement in tremors, mobility, and other movement symptoms after undergoing a minimally invasive procedure using focused ultrasound, a study published in the New England Journal of Medicine shows.

Deep brain stimulation (DBS) has become the main surgical treatment for people with PD who do not fully respond to levodopa. It involves the invasive surgical placement of tiny wires into the targeted brain area, which is then stimulated by sending electrical signals through the wires. Focused ultrasound is a treatment that emits high-intensity sound waves into the brain, guided by magnetic resonance imaging (MRI). Where these waves cross, they create high energy, which creates heat, destroying a specific area in the brain connected to tremor. It is considered non-invasive because it does not involve incisions or holes in the skull.

Both treatments have pros and cons.

• Focused ultrasound is non-invasive. It does not require additional adjustments and creates a permanent change.
• DBS is an invasive surgery that allows for adjustments as movement symptoms worsen through the course of Parkinson’s, even years after surgery. DBS can still be an option for those who undergo focused ultrasound if the disease continues to progress.

The U.S. Food and Drug Administration (FDA) approved focused ultrasound as a Parkinson’s treatment for those with movement symptoms mainly on one side of the body. However, most people with Parkinson’s have movement symptoms on both sides of the body. This study included people who have symptoms on both sides of the body.

About the Study & Results

The focused ultrasound targets a part of the brain called the globus pallidus internus (GPI), which is part of the basal ganglia, a network of brain structures that controls movement. In Parkinson’s, the loss of dopamine-producing neurons disrupts the normal functioning of the basal ganglia. This can ultimately lead to abnormal activity in the GPI and can contribute to the movement symptoms of Parkinson’s.

This study examined the safety and efficacy of focused ultrasound of the GPI in a randomized trial of 94 participants with PD movement symptoms. Only the side of the brain opposite the participant’s most symptomatic side was treated. Of the 94 participants, 69 were randomly selected to undergo the procedure, with 25 receiving the false treatment as a control.

Each participant received a clinical assessment for the severity and progression of their Parkinson's before and after treatment. Nearly 70% of participants in the treatment group had improvements in symptoms after three months of follow-up, compared to 32% in the control group who had an inactive procedure without focused ultrasound.

One year later, a follow-up assessment tracked 60 of the original 69 participants and found that 66% of those who received treatment and initial improvement in symptoms continued to have a positive response to the treatment. Additionally, of the 25 participants who initially had a placebo treatment, 20 chose to undergo treatment three months later. Of the 20 that chose treatment, 70% had a positive response at three months, and 57% had continued success one year later.

A third of the participants had no side effects. Among those who did, most participants experienced only some mild to moderate symptoms, including headaches, dizziness and nausea. However, one person experienced a serious complication related to the procedure: a nonfatal pulmonary embolism. At the three months check-up, adverse reactions were mild to moderate and included slurred speech, disturbances in walking, loss of taste, visual disturbance and facial weakness. 

Highlights

• The clinical trial used focused ultrasound to target movement symptoms of participants with Parkinson’s with the goal of improving them.
• Nearly 70% of participants in the treatment group responded successfully to treatment after three months of follow-up, compared to 32% in the control group who did now undergo the focused ultrasound.
• About 66% of participants in the treatment group who had initial success continued to have a positive response from the treatment a year later.

What does this mean?

This treatment may be effective for improving physical symptoms of Parkinson’s. However, the long-term effects of the procedure are still not known. All participants in the study will be followed for five years to assess the effects and long-term safety of the procedure.

What do these findings mean to the people with PD right now?

Although approved by the FDA, it will be years before we know the long-term effectiveness and impacts of focused ultrasound as a PD treatment. The Parkinson’s Foundation encourages people with PD to work with a movement disorders specialist to make sure a focused ultrasound is a good option.

There are an increasing number of sites offering focused ultrasound for Parkinson’s across the country. For a list of sites that offer the treatment, visit the Focused Ultrasound Foundation website. Be sure to ask about the site’s experience with treating Parkinson’s disease, specifically.

Of note, focused ultrasound is not universally covered by Medicare — eligibility and region vary when it comes to Medicare reimbursement. It will take time for the procedure to become more widely available and to be covered by insurance. Directly contact the center offering focused ultrasound in your area for specific information about insurance coverage.

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 below, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Other Surgical Options
• Non-pharmaceutical Treatments for PD: DBS and Focused Ultrasound
• Surgical Options: A Treatment Guide to Parkinson's Disease - Updated

As Parkinson’s research advances, experts are discussing how to biologically define and possibly classify Parkinson’s disease.                                   

Right now, a discussion is gaining momentum among scientists researching Parkinson’s disease (PD) to use the latest advances in research to define Parkinson’s for the first time, based upon its biological signature. But why? And more importantly, what does this mean for those living with PD right now and the 90,000 people diagnosed every year?

Currently, diagnosing Parkinson’s is a mix of art and science. A PD diagnosis is made when a doctor weighs the evidence contained in a combination of symptoms (clinical hallmarks), response to dopamine therapy and use of in-office exams. Sometimes, brain imaging or a skin biopsy can be used to help support the diagnosis. Ultimately, there is no single test that can unequivocally confirm a person has Parkinson’s and no test to track disease progression.

Why Scientists Believe We Need to Define Parkinson’s

Parkinson’s research is advancing. We are getting closer to being able to use a biomarker to diagnose Parkinson’s. For example, high blood pressure is a biomarker for hypertension and blood glucose levels are biomarkers for diabetes. For PD, reliable biomarkers could one day potentially lead to an earlier PD diagnosis and help researchers design and test therapies that might slow or stop the disease.

For PD, the protein alpha-synuclein can act as a biomarker. Years of research show that this protein is involved in most but not all PD cases. While the alpha-synuclein protein has a useful role in the body, in PD, it becomes misfolded and damaged. This misfolding, much like a crumpled piece of paper, is associated with the damage of brain cells and the formation of alpha-synuclein clumps called Lewy bodies. These protein depositions pathologically define PD and the related disease, Lewy Body Disease or Dementia with Lewy Bodies. 

We know from pivotal research, some of which was funded by the Parkinson’s Foundation and published in 2008, that misfolded alpha-synuclein can spread in the brain. The alpha-synuclein then acts as a “seed,” causing normal alpha-synuclein to form new clumps that change how brain cells work.

Recent advancements have opened the door for scientists to find misfolded alpha-synuclein in cerebrospinal fluid (CSF) of people with PD. This method for detecting abnormal alpha-synuclein is called alpha-synuclein seed amplification assay (SAA). In 2023, the accuracy of this approach was published. Recently in Nature, researchers from Japan published a blood-based approach to measure alpha synuclein.

Scientists believe the synuclein seed amplification assay could be an effective way to identify Parkinson’s in its “preclinical” stage, years before symptoms appear. However, the assay has its limitations. The testing method is not yet widely standardized and not all scientists have achieved the same results. The fluid required for the testing uses a spinal tap, which is a procedure that removes a small amount of cerebrospinal fluid and is not easily collected. The hope is that more serum and blood-based approaches will replace spinal fluid.

Also, the SAA assay test only confirms the presence of misfolded alpha-synuclein — it does not pick up all cases of Parkinson’s, especially cases of the LRRK2 genetic variant. Results cannot help scientists or doctors track disease progression, nor can it determine if someone who has misfolded alpha-synuclein — but no PD symptoms — will develop PD. Nevertheless, scientists — including those funded by the Parkinson’s Foundation — are working to overcome these limitations with the goal of re-engineering the SAA biomarker test to use a blood draw instead of CSF.

Scientists believe that using biomarkers to biologically define Parkinson’s can help identify early PD with more certainty and help to advance clinical trials. For now, alpha-synuclein is the first validated biomarker to be used in early clinical research. Researchers are already working on finding other PD biomarkers (through an MRI, skin biopsy and others) that can be used to diagnose PD and monitor its progression.

What’s in a name?

With the advancements being made in PD biomarkers, researchers are beginning to think about a new way of describing or “classifying” PD. This would provide a standardized way for researchers, doctors and epidemiologists (those who study disease) to describe PD and its various stages. This is in contrast with how we study PD right now, as Parkinson’s does not have a singular disease classification.

Because Parkinson’s is tied to the abnormal clumping of alpha-synuclein in the brain, some propose reframing “Parkinson’s disease” into a larger disease category. Two new approaches have recently been proposed:

1.  Neuronal Synuclein Disease

The first presumes that alpha-synuclein is an effective, and potentially the only, biomarker to define diseases where alpha-synuclein plays a role, such as Parkinson’s and Lewy Body Disease (LBD). Researchers propose to use “Neuronal synuclein disease” as an umbrella term to describe PD and its alpha-synuclein related diseases as part of a proposed disease staging system (Simuni et al., 2024). This classification requires use of cerebrospinal fluid (CSF) and DaT brain scanning.

2.  SynNeurGe

The second approach to classifying PD also relies on using alpha-synuclein as a biomarker but incorporates other disease features in classifying the disease (Höglinger et al., 2024). Here, researchers also use brain imaging and genetic status to define what is PD and what is not. The researchers do not propose changing the name of Parkinson’s disease but add the classification scheme, called “SynNeurGe” (pronounced synergy) alongside it.

Importantly, these two proposed approaches for defining PD lay important groundwork but also “underscores substantial knowledge gaps that deserve further study,” (Darweesh et al., 2024).

What This Means for The PD Community Right Now

The future of PD research lies in being able to define the disease based on a biological basis, which marks the beginning of more efficient ways to define, diagnose and treat PD. However, the work towards disease classification or a biological definition of PD will take time. Right now, these discussions do not impact how Parkinson’s is currently diagnosed or treated.

As researchers debate the merits of each approach (or even continue to propose new ones), it will take time to reach a consensus and to implement any changes to how PD is classified. If a new classification scheme is implemented, the likely first impact will be how clinical trials are conducted. Researchers may choose to fill research studies with participants who have received a diagnosis via the biomarker test, as they may respond better to certain drug treatments.

“Tying Parkinson’s disease to a new classification or definition is a new, evolving approach that will take time to first develop in research and then move into general use in the clinic. There will be ups and downs along the way, but with feedback from the community and continued advances in research the overall result will hopefully mean better care for people living with PD,” said James Beck, PhD, Parkinson’s Foundation Chief Scientific Officer.

In the meantime, it remains imperative that people who suspect they have Parkinson’s should be aware of the early signs and speak to their doctor. An early diagnosis will always remain the best course of treatment to maintain a high quality of life.

As research advances towards precision medicine, genetic testing is an important way researchers can help advance the field towards better treatments and diagnosis. Studies like PD GENEration: Mapping the Future of Parkinson's Disease are empowering people with Parkinson’s with their genetic status at no cost. These results can be shared with their doctor to guide treatment.

Here For the Parkinson’s Community

As this process unfolds, the Parkinson’s Foundation will continue to support innovative scientific research that improves life for people with PD and report any new information to our community. The Foundation continues to serve as a trusted ally to the Parkinson’s community, providing information that can help people navigate every stage of the disease.

Learn More

Learn more about advances in research by visiting the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636) for answers to your Parkinson’s questions.

• A New Test Could Detect Parkinson’s Before Symptoms Appear

• What is a Disease Modifying Therapy in PD?

• Finding A Cure