Inside the Science: Parkinson's Research Today

Parkinson’s disease (PD) research is advancing rapidly, with breakthroughs on the horizon that could transform treatment and offer hope to millions.

Three key research areas are among the most active and promising: alpha-synuclein aggregation, mitochondrial dysfunction and neuroinflammation. Learn what these terms mean, where the science is headed and how advances in these areas may lead to new treatments and disease-modifying therapies.

This article is based on a Parkinson’s Foundation Expert Briefing exploring advances in Parkinson’s research hosted by Laurie Sanders, PhD, Associate Professor, Neurology and Pathology, Movement Disorders and Translational Brain Sciences divisions, at Duke University School of Medicine, a Parkinson's Foundation Center of Excellence.

Urgency is Driving Research

The pressing need to crack the code behind the causes of Parkinson’s has never been greater. Though there are a wide variety of treatments to manage PD symptoms, there is no cure. More than 11 million people worldwide are living with Parkinson’s, including more than 1 million in the U.S.

PD cases are expected to exceed 25 million globally by 2050. The economic impact is staggering: Parkinson's cost the U.S. $82.2 billion in 2024. More than $23 billion went toward direct medical costs, while nearly $60 billion reflects indirect costs, including lost income and burdens on care partners.

The determination to solve the Parkinson’s mystery is possibly best reflected in the number of current studies in the research pipeline. The National Institutes of Health’s (NIH) ClinicalTrials.gov shows more than 200 Parkinson’s-related clinical trials either actively recruiting or about to recruit. In addition, foundational research that advances our overall understanding of Parkinson’s biology continues to take place, especially in the following areas.

3 Key Parkinson’s Research Areas Right Now

Parkinson’s is complex, as scientists believe a combination of environmental and genetic factors are the cause of Parkinson's. Research requires attacking the problem from multiple angles. Studies suggest the development and progression of Parkinson’s involves interactions among three key biological areas:

1. Protein Aggregation: Alpha-synuclein

Parkinson’s involves the loss of dopamine-producing neurons and a buildup of alpha-synuclein, a normally useful protein found in the brain that helps brain cells communicate. There is very strong genetic evidence linking alpha-synuclein to Parkinson’s disease via the SNCA gene, which was the first PD-associated gene to be identified.

Alpha-synuclein becomes problematic when it misfolds, gathering into clumps called Lewy bodies that can spread between brain cells. Many PD treatments target and remove these alpha-synuclein clumps. However, while Lewy bodies are a hallmark of Parkinson’s, there is still some controversy over whether they are part of the Parkinson’s problem or act as a protective factor.

2. Mitochondrial Dysfunction

Mitochondria are energy powerhouses that are critically important to good health. They malfunction in Parkinson’s, impacting cellular energy and contributing to cell death. Neurons — brain cells that send electrical and chemical communications — are especially vulnerable to mitochondrial dysfunction.

Certain gene mutations can impact mitochondrial function, as can environmental toxins like pesticides (such as paraquat).

Genetic risk factors, including PINK1 and PRKN that are specifically related to mitochondria, can also influence PD development and severity.

3. Brain Inflammation

When combined with the other two factors, studies suggest that brain inflammation (the brain’s protective response to harm, which may become overstimulated in Parkinson’s) can make those problems worse. In addition, inflammation can weaken the blood-brain barrier that may allow immune cells from the blood to enter the brain, which can accelerate neurodegeneration.

Advances Accelerating Parkinson’s Research

Once considered solely a movement disorder, we now know Parkinson’s is a multisystem disease that can affect the whole body — including urinary problems, gut issues and changes to thinking, sleep and mood.

Patient engagement is essential for PD research progress. Major influences that deepen our understanding of PD risk include studies with global reach like PD GENEration: Powered by the Parkinson’s Foundation, which is providing insights as to how Parkinson’s is tied to genetics through providing genetic testing and counseling to people with a confirmed PD diagnosis. Importantly, the biological discoveries made about Parkinson’s via genetic testing may also apply to Parkinson’s cases that do not have a known genetic link.

New tools are being developed that hold the possibility to detect Parkinson’s earlier, better understand its progression and help track the effectiveness of PD therapies. These tools include:

• Brain imaging to help researchers visualize the spread of Parkinson’s, identify specific areas of brain pathology and increase diagnosis accuracy including advances in developing positron emission tomography (PET) ligands, high-resolution MRI and diffusion imaging.

• Ultrasensitive lab tests to measure new Parkinson’s biomarkers from spinal fluid and other fluids such as blood. These tests include:

  • alpha-synuclein seeding assays (SAAs) to detect tiny amounts of misfolded alpha-synuclein.

  • tests that can identify neurodegeneration, such as for the protein neurofilament light, which has been linked to PD, and other markers of inflammation.

  • Tests for mitochondrial DNA damage, such as MitoDNADX, a recent blood test developed by Duke University researchers for use as a potential biomarker in PD.

• Improved disease models, including:

  • induced pluripotent stem cells (iPSCs), developed by recoding cells from people with PD to become dopamine neurons, allowing for the study of PD-related cell dysfunction in patient tissue. 

  • organoids, which are miniature brains that allow scientists to study Parkinson’s mechanisms and test possible therapies.

  • refined animal models, that are genetically engineered to better model Parkinson’s symptoms.

Research Breakthroughs and Targets

Scientists are investigating ways to slow or halt Parkinson’s, identify people for participation in relevant PD trials and deliver targeted treatments.

Nearly 100 forms of alpha-synuclein have been identified, with research to determine which are most toxic. As scientists dig deeper into PD progression, they have also discovered alpha-synuclein pathology along the GI tract of people with PD.

Parkinson’s and GI research is expanding, including through the Gut-Brain Communication in Parkinson’s Disease Consortium, a joint effort between the NIH and the Duke Clinical Research Institute.

Many people with Parkinson’s also experience the buildup of other proteins such as Beta-amyloid plaques and Tau tangles, key hallmarks of Alzheimer’s disease. One promising study under way is exploring whether oral therapy buntanetap is safe for long-term use in people with PD. Buntanetap aims to reduce other toxic proteins. Investigational Parkinson’s treatments also include immunotherapies that use antibodies to target harmful protein clumps and approaches that help cells manage or remove misfolded proteins.

Mutations in the GBA1 gene, a common genetic risk factor for Parkinson’s, reduce the activity of the glucocerebrosidase enzyme, contributing to alpha-synuclein buildup. New treatments are being developed to boost glucocerebrosidase activity to help cells more effectively remove harmful buildup. A variety of therapies are also in the research pipeline to rescue mitochondrial function.

The Way Forward

Parkinson’s research is fundamental for progress toward new disease-modifying therapies that can slow or stop disease progression. By improving our understanding of the ways in which alpha-synuclein, mitochondrial dysfunction and inflammation interact, we get closer to having personalized, precision-medicine treatments for PD. When we combine this knowledge with patient participation in research, breakthroughs in technology and new biomarker discoveries, we continue to advance closer to a cure for Parkinson’s.

How to get involved:

• Visit Join A Study to explore current clinical trials.

• Become a Research Advocate to ensure more efficient, effective Parkinson’s research.

• Learn how PD Trial Navigator is connecting PD GENEration participants to clinical trials that are relevant to them.