April is Parkinson’s Disease Awareness Month, chosen because it is the birth month of James Parkinson, who first identified the symptoms of Parkinson’s disease more than 200 years ago. Since then, we have made considerable progress towards understanding what causes the motor symptoms we most associate with Parkinson’s disease (PD), and along the way, we have begun to appreciate a broad spectrum of non-motor symptoms that were not initially recognized as part of the disease. NIH scientists discovered that the Lewy Body, a signature abnormality of PD seen under the microscope in brain cells, was composed of clumps of a protein called synuclein. Most recently, scientists have developed a test to detect the abnormal form of synuclein in the fluid that surrounds the brain. This fluid can be obtained by a spinal tap, and NINDS-supported scientists are working to modify the test for more accessible samples (for example, from skin or saliva). The test requires greater validation, but current data suggests it has good accuracy in diagnosing this form of PD, even years before motor symptoms begin. Such a test would offer the exciting possibility to detect and treat the underlying biology of PD early enough that disabling symptoms never occur. Yet, we have much more to achieve through research to better understand and develop means to prevent or slow down the progression of PD. In fiscal year 2022, NIH funded $259 million in PD research. As the primary NIH institute for PD research, NINDS supports many basic, translational, and clinical research programs looking at new ways to diagnose, treat, and hopefully halt the disease.
Although treatments available today can lessen some symptoms of PD, they are most effective in the early stages of PD. Their effectiveness decreases as the disease progresses over time, and interventions to prevent the progression of the disease do not yet exist. NINDS’s commitment to supporting research on PD includes deep brain stimulation (DBS) for PD, as well as current NINDS-supported research both through the Morris K. Udall Centers for Excellence in Parkinson’s Disease program and the NIH BRAIN Initiative.
Another intervention that has received considerable attention in recent years is exercise. It’s been shown that exercise can improve PD symptoms, and there is some evidence now suggesting it could be disease-modifying as well. NINDS currently supports the SPARX3 phase III trial, which is studying the effects of aerobic exercise on the progression of PD. Encompassing 25 sites across the United States and Canada, SPARX3 is currently enrolling patients, and is the first trial to look at moderate- and high-intensity aerobic exercise on disease progression in people with untreated PD.
One of the major challenges in moving PD therapeutics forward is the lack of biomarkers for disease progression. To address this, NINDS supports programs such as the Parkinson’s Disease Biomarkers Program (PDBP), part of the NIH Accelerating Medicines Partnership (AMP PD). NINDS, grantees, disease organizations and pharmaceutical industry staff work together in an effort to identify and validate biomarkers and drug targets to advance the development of treatments for PD.
PDBP was developed to accelerate the pace of new biomarker discovery, and to advance therapeutic development for PD by providing a platform to integrate ongoing biomarker efforts while standardizing the management and collection of data. PDBP currently supports nine studies looking at Parkinson’s disease and similar disorders like Lewy body dementia (LBD), progressive supranuclear palsy, and multisystem atrophy, which can sometimes present with motor and behavioral changes similar to PD. Three of the most recent studies are focused on LBD and its connections with PD. Two (NS100610 and NS100620) are looking at new ways of imaging the brain to better observe symptoms and symptom progression. The third (NS128433) takes a proteomics approach to the search for new biomarkers in the blood and cerebrospinal fluid of people living with LBD.
NINDS is also helping to catalyze the discovery of new biomarkers for PD through the AMP PD program. As a partnership between government, non-profit, and industry and managed through the Foundation for the National Institutes of Health (FNIH), AMP PD provides a data portal to bring clinical, genomic, transcriptomic, and proteomic data together to be housed under one virtual “roof.” This enables researchers to collaborate on harmonized data in a cloud-based environment that reduces traditional barriers to these types of complex analyses such as the need for vast computing power and data siloes. The data within the AMP PD platform comes from a variety of sources, including PDBP, and is continually being updated. The most recent data release, in February 2023, brought in new data from the Global Parkinson’s Genetics Program (GP2)—a program funded by the Aligning Science Across Parkinson’s (ASAP) initiative—and additional targeted proteomics, including data from PDBP. To learn more about AMP PD or to register for the Knowledge Portal, I encourage you to visit the AMP PD website.
In addition to developing new ways of monitoring the progression of PD, NINDS also actively supports clinical efforts to slow or halt disease progression. NeuroNEXT is a clinical trial network funded by NINDS since 2011 to accelerate the pace of drug and other treatment development for neurological disorders, with a particular emphasis on phase II clinical trials. NeuroNEXT currently supports ENLITE PD, a trial investigating the use of light therapy to treat PD-related sleep disturbances. This project brings together 25 institutions to focus on a specific non-motor symptom of PD: disrupted sleep and alertness. These symptoms, which affect as many as 90% of people living with PD, contribute significantly to decreased quality of life, mood and cognitive impairment, and can increase the risk of accidents, morbidity, and mortality.
This year is a notable milestone, marking the 25th anniversary of the NINDS Morris K. Udall Centers of Excellence for Parkinson’s Disease Research. This program was established in honor of former Congressman Morris K. Udall (D-Ariz.), who was diagnosed with PD in 1979 and remained active in Congress until his retirement in 1991. Udall Centers use an interdisciplinary and team-based approach to improve understanding of the fundamental causes of PD and to inform ways to improve both the diagnosis and treatment of people living with PD and related neurodegenerative disorders.
Today, the NINDS Udall Centers program conducts a broad range of research that includes understanding PD-induced changes in brain circuits to the role of the immune system in PD to developing novel ways to measure and evaluate PD symptoms. Prior work funded by the Udall Centers program has led to several discoveries, including therapeutics currently being tested in clinical trials. Udall Centers also contribute to ongoing NINDS PD programs, including sharing biospecimens and data through PDBP and AMP PD, as well as to global efforts in PD research and treatment.
In addition to significant research advances, another key success of the Udall Centers program has been a commitment to career development of Center investigators and trainees, fostering the next generation of PD researchers. Additionally, Udall Centers incorporate the voice of people with lived experiences into their advisory committees and lead pro-active outreach to the local patient and advocacy community. This outreach helps to inform and engage the public in learning about recent advances in PD research as well as opportunities to participate in clinical studies.
Finally, NINDS is also striving to address health disparities in PD. Understanding the genetics behind PD requires a full picture of everyone who is affected by the disorder; however, the vast majority of PD genetic samples we have to study comes from people of European descent. Disparities also exist in access to care and research opportunities. NINDS partners with the Fogarty International Center on the Global Brain and Nervous System Disorders research program to support research programs and scientists in low- and middle-income countries.
This April, we are reminded of the tremendous progress we have made over the years in our understanding of PD, but we must also keep in mind the challenges we still face. Through the programs I have highlighted today and other studies, NINDS is committed to unlocking the mysteries still surrounding PD and paving the way towards new therapies and strategies to halt or prevent this disease.