5 areas to watch in Parkinson’s research

As a scientist who studies Parkinson’s disease, I often say that my job is to put myself out of business. That means getting to a point where we have effective ways to slow, stop or reverse the disease, something not possible with current therapies.

Today, Parkinson’s typically is diagnosed by evaluating symptoms against a set of clinical criteria. Treatment focuses on managing symptoms rather than targeting the disease’s underlying causes.

We’re working to change this reality through rigorous research that translates into new options for people with Parkinson’s. But what would such a future look like?

It would mean having effective tools, like a blood test, that enable us to diagnose Parkinson’s early, ideally before symptoms appear. We would then treat the disease with personalized therapies tailored to an individual’s specific case. This approach would do more than address symptoms — it would stop the disease from progressing or slow it to the point that symptoms never fully develop.

Although we are not there yet, we are well on our way to a world in which Parkinson’s is caught early and treated in ways that stave off progression. Here are five areas to watch for breakthroughs in the coming years.

Understanding genetic risk — and using it to improve treatment

Every cell in the body contains an almost identical copy of DNA, the spiraling molecule that encompasses the instructions for life. You can think of DNA as a cookbook and genes, which are segments of DNA, as recipes. These “recipes” result in proteins, which carry out virtually every function in the body.

Changes in genes or in the way genes are used can lead to too much or too little protein production, or cause proteins to function improperly. When this happens, proteins cannot do their jobs, and the systems that keep us healthy begin to break down.

Up to 10% of Parkinson’s cases are directly linked to genetic changes passed down through families. The other 90% of cases are likely caused by a mix of age-related changes, genetic risk and environmental factors such as pesticide exposure.

Since the first Parkinson’s-related gene was discovered in 1997, scientists have identified more than 20 genes that cause familial Parkinson’s and more than 200 genes that may affect risk.¹ Every new gene added to the list is an opportunity to better understand — and potentially better diagnose and treat — Parkinson’s. We can study how these genes influence Parkinson’s, how they interact to affect risk and how they are affected by other factors, such as chronic infections or pesticide exposure.

One of the biggest challenges in developing new treatments for Parkinson’s is its variation. In most cases, each person has their own unique mix of factors that contribute to the disease. Identifying and understanding Parkinson’s-related genes offers a powerful opportunity to better define these different subtypes and design personalized treatments.

Here’s an example. LRRK2 and GBA1 are two genes commonly linked to Parkinson’s, but they affect the body in different ways. Changes in LRRK2 can disrupt a cell’s ability to clear out waste, leading to damage over time. Changes in GBA1 reduce levels of a helpful protein called GCase, allowing harmful proteins to build up. In the future, this distinction could guide treatment. Someone with a LRRK2 mutation might benefit from a medication that reduces LRRK2 activity, while someone with a GBA mutation might need a treatment that boosts GCase function. Matching therapies to these underlying genetic factors could make treatments more effective and help avoid therapies that are unlikely to work for a given person.  

Identifying biomarkers to diagnose Parkinson’s earlier and with more precision

Biomarkers are measurable indicators that give us information about what’s happening in the body. Here are a few examples:

• Measuring body temperature to detect fever
• Blood sugar levels to diagnose and monitor diabetes
• BRCA gene mutations to assess breast cancer risk and guide treatment

Identifying biomarkers for Parkinson’s disease could enable earlier detection and diagnosis, which means earlier treatment with future medications that slow progression. Biomarkers also could make it easier to track disease progression and evaluate whether treatments are working. Importantly, they could help better define different types of the disease and tailor treatment to be more effective.

Certain gene changes, such as those in LRRK2 and GBA, are important biomarkers. Another key biomarker is alpha-synuclein, a protein that can become misshapen and form clumps in brain cells called Lewy bodies. Lewy bodies are a hallmark of Parkinson’s disease and are thought to disrupt the “machinery” needed for normal function in brain cells that regulate movement. The loss of these important cells contributes to Parkinson’s symptoms and disease progression.

Scientists around the world are working to identify new biomarkers and optimize existing ones. The Parkinson’s Progression Markers Initiative (PPMI) is a landmark clinical study spearheaded by the Michael J. Fox Foundation for Parkinson’s Research. Since 2010, it has transformed our understanding of Parkinson’s by providing the data and tools needed to drive discovery. None of this work would be possible without the Parkinson’s community’s steadfast participation and support.

In 2023, scientists working with PPMI used a technique called alpha-synuclein seed amplification assay to detect alpha-synuclein in spinal fluid. For the first time, they were able to identify Parkinson’s disease in its earliest stages. Ongoing research aims to adapt the test for use with blood samples or simple skin scrapes, which are less invasive than spinal taps. The test is not yet available in doctors’ offices but I’m hopeful it will be used to diagnose the disease in the future.  

Here at VAI, our West Michigan Neurodegenerative Diseases (MiND) Program searches for biomarkers by collaborating with local hospitals to collect blood samples from donors. We then analyze these critical samples for gene changes, which helps us understand the landscape of Parkinson’s disease in West Michigan. The MiND Program also manages the VAI Brain Bank, which houses donated brains from people with and without neurodegenerative disease. These selfless donors are powering advances by ensuring scientists have the samples required to study Parkinson’s, search for biomarkers and make discoveries that change lives. Learn more about this important work by visiting the MiND page ➔

Studying Parkinson’s with more depth and precision

Advances in technology help us better study Parkinson’s, from investigating its causes to identifying ways to potentially slow its progression.

Induced pluripotent stem cells (iPSCs) are one of these tools. iPSCs are created by “reprogramming” blood or skin cells back to an earlier, blank-slate state. From there, iPSCs can be transformed into other cell types, making them powerful tools for research.

This kind of innovation is particularly important in Parkinson’s. Unlike many other diseases, there are no simple, low-risk ways to biopsy and study brain tissue in people living with Parkinson’s. iPSCs help solve this problem: They allow us to grow neurons that share the same genetics as the person from which they came — no brain biopsy required.

These “mini brains in a dish” helps us do two important things: 1.) study how Parkinson’s develops in an individual’s brain cells, and 2.) test potential new therapies to see how a person’s specific type of Parkinson’s may respond.

Although still relatively new, iPSCs have the potential to be game changers. Ongoing research at VAI and in labs around the world are using this powerful technology to develop improved ways to assess disease progression and evaluate personalized therapies.

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Learn more about VAI’s iPSC platform ➔

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Fixing problems with proteins

Alpha-synuclein is a protein found throughout the human body. In Parkinson’s, it becomes misshapen and sticks together forming clumps called Lewy bodies. These clumps interfere with dopamine-producing brain cells in the brain, causing them to malfunction and eventually die. Dopamine is an important chemical messenger that regulates movement, and loss of the cells that produce it cause many of Parkinson’s hallmark movement symptoms.

Because of its central role in Parkinson’s, targeting alpha-synuclein holds immense promise for designing more effective treatments. Many potential therapies are in development or the clinical trial pipeline, including medications that:

• Reduce alpha-synuclein production
• Prevent misfolded alpha-synuclein from aggregating into Lewy bodies
• Break down and clear out alpha-synuclein and Lewy bodies
• Harness the immune system to target and eliminate Lewy bodies

Another exciting avenue is structural biology. Structural biologists study how the shape of molecules influences their function. When proteins like alpha-synuclein become misshapen, they lose their ability to do their jobs, just like a broken key no longer fits into a lock.

At VAI, our scientists use a powerful technique called cryo-electron microscopy to visualize proteins and molecular complexes involved in Parkinson’s and Alzheimer’s at the near-atomic level. The resulting insights offer “blueprints” for building better medications.

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Learn more about structural biology at VAI ➔

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Evaluating ways to slow or stop progression

Before new treatments can be used, they must go through clinical trials to ensure they are safe and effective. Many potential Parkinson’s therapies in clinical trials today aim to slow or stop disease progression, a shift from current therapies that primarily manage symptoms.

The International Linked Clinical Trials (iLCT) Program is a great example of this critical work. Spearheaded by Cure Parkinson’s and VAI, iLCT evaluates medications developed for other diseases as potential therapies for Parkinson’s. The program then supports clinical trials to assess whether these medications can address the disease’s underlying causes.

You may be wondering how a medication that treats cough or diabetes can impact Parkinson’s. It’s a fair question with an answer grounded in science. Although they present differently, many diseases share similar underlying mechanisms. As a result, one medication can have different uses across different diseases. This approach, called drug repurposing, can save precious time and resources because it relies on medications that already have passed rigorous safety tests.

Earlier this year, VAI joined a collaborative group of funders to announce the world’s largest clinical trial of potential Parkinson’s disease therapies to date. The Edmond J. Safra Accelerating Clinical Trials in Parkinson’s Disease (EJS ACT-PD) trial uses a flexible design that enables the clinical team to evaluate multiple potential treatments in parallel. As a result, the time required to test candidate therapies may be shortened by up to three years. The trial, led by researchers at University College London and Newcastle University, is recruiting up to 1,600 people across 40 hospitals in the United Kingdom. Learn more about EJS ACT-PD ➔

Clinical trials are made possible by the participants — people with and without Parkinson’s who take part in this vital research. It is an honor to partner with them as we pursue new therapies.

Closing thoughts

Our understanding of Parkinson’s is deeper than ever before, but we still have much more work to do. Research — driven by new discoveries, collaboration and support from the Parkinson’s community — is revealing new opportunities to slow or stop progression.

In the coming years, I’m confident that we will shift from a symptom-focused approach to one centered on early detection and disease-modifying treatments. The road may be challenging but together, we are getting closer to changing the course of Parkinson’s treatment, improving quality of life and building a healthier future.