The Michael J. Fox Foundation for Parkinson’s Research (MJFF) invests nearly 90% of its spending to find a cure for the debilitating neurodegenerative disease, totaling more than $800 million since its founding in 2000, including $100 million in 2017.

MJFF CEO Todd Sherer, Ph.D., notes the organization “is the world’s largest non-profit funder of Parkinson’s disease research” and he anticipates significant progress over the next five years in the development of therapies “to slow or stop disease progression.”

The organization has already made substantial progress. The causes of Parkinson’s are believed to be a combination of genetic predisposition and environmental triggers, Sherer says, and research has uncovered links with other neurological conditions. “We are also finding genetic similarities between Parkinson’s and non-brain diseases, such as Gaucher and Crohn’s, that could help us to better understand and treat across conditions,” he adds.

More than 1 million people are impacted by Parkinson’s disease in North America and 6 million worldwide, according to the Global Burden of Disease Study. In the US, 60,000 new cases are diagnosed each year.

Sherer became MJFF’s CEO in 2011. He directs the organization’s research strategy, and is responsible for its overall scientific and fundraising direction. He joined the foundation fulltime in 2004 as associate director of research programs after receiving a grant the year before to support his postdoctoral research at Emory University examining the role of environmental factors in Parkinson’s disease.

Sherer, who is recognized worldwide as an expert on Parkinson’s and the development of new therapies to treat the illness, earned his Ph.D. in neuroscience from the University of Virginia and holds a bachelor’s degree in psychology from Duke University.

In a recent interview with WuXi AppTec Communications, Sherer discussed the scientific advances in understanding Parkinson’s disease, the challenges facing drug developers, and the progress being made in finding a cure.

WuXi’s interview with Sherer is part of an exclusive series spotlighting the inside perspectives of thought leaders on topics shaping the future of new medicines.

WuXi: Is Parkinson’s disease caused by genetic abnormalities, environmental factors or a combination of the two?

Todd Sherer: A little more than 20 years ago, scientists believed Parkinson’s had no genetic component. However, in the past two decades, the field has built an appreciation for the role of genetics and its interplay with environmental and lifestyle factors to determine Parkinson’s risk. In most cases, genetic predisposition and an environmental trigger likely lead to Parkinson’s.

WuXi: How would you describe the evolution of Parkinson’s disease research?

Todd Sherer: Parkinson’s research has undergone a genetics revolution in the past 20 years — opening doors to new understanding of risk, onset and progression and pointing to therapeutic targets and biomarker candidates now doggedly pursued by scientists. In addition, the field has a growing understanding of Parkinson’s as more than a movement disorder. Scientists and clinicians now recognize the many non-motor aspects of the disease – for example, mood disorders, cognitive impairment and autonomic dysfunction – and are developing therapies with targets outside the dopamine system.

WuXi: What are researchers learning about the causes of Parkinson’s disease and are there implications for other neurological disorders?

Todd Sherer: A handful of neurodegenerative diseases such as Lewy body dementia and multiple system atrophy share the hallmark pathology of Parkinson’s – accumulation of the protein alpha-synuclein. Findings on the biological processes that lead to that aggregation and its spread will inform the development of treatments for people with synucleinopathies. We are also finding genetic similarities between Parkinson’s and non-brain diseases such as Gaucher and Crohn’s that could help us to better understand and treat across conditions.

WuXi: Is the US National Institutes of Health’s (NIH) Brain Initiative having an impact on Parkinson’s disease research?

Todd Sherer: Many questions remain around brain function and diseases. The NIH Brain Initiative has directed critical research funds, attention and expertise to understanding this complex organ and treating its dysfunction.

WuXi: How does The Michael J. Fox Foundation (MJFF) support Parkinson’s disease research and drug development?

Todd Sherer: The Michael J. Fox Foundation is the world’s largest non-profit funder of Parkinson’s disease research. Twice per year we issue an open call for applications to funding programs that advance our top research priorities.

In addition to granting funds, we build infrastructure and provide resources to help scientists accelerate their projects. Our foundation has developed and characterized an extensive catalog of research tools such as assays, antibodies and models, which are available quickly and at cost to researchers in academia and industry.

Other resources for the scientific community, both industry and academia, include open-access to de-identified study data, biosamples available for request, and clinical trial recruitment and retention support.

WuXi: What is the best strategy for developing Parkinson’s disease treatments?

Todd Sherer: A burgeoning area of Parkinson’s drug development is precision medicine. For example, we might target treatments to dysfunction linked to genetic mutations present in a subset of the population. This strategy of directing treatments based on biology and etiology, rather than solely clinical presentation, will hopefully yield success in our efforts to slow and stop disease progression.

WuXi: What are the major challenges in treating Parkinson’s disease?

Todd Sherer: Parkinson’s clinical and biological variability has challenged drug development. We need objective, selective biomarker tests to predict, diagnose and monitor Parkinson’s disease and test the impact of therapeutic interventions. MJFF sponsors the Parkinson’s Progression Markers Initiative, a large-scale longitudinal study to identify and validate biomarkers of the disease. Study data, open-access for all qualified researchers from industry and academia, has been downloaded more than 1.5 million times from the scientific community for additional analysis.

WuXi: What scientific breakthroughs are needed to better understand the causes and progression of Parkinson’s disease?

Todd Sherer: Expansion of large-scale observational studies such as the MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI) are helping build the infrastructure for scientific breakthroughs. PPMI is collecting comprehensive data from patients over many years, including clinical assessments, imaging, fluids and information from wearables and mobile devices. Additionally, technology is enabling in-depth cellular profiling and analysis. The challenge now is in translating that data to actionable insights that can point to Parkinson’s causes and biomarkers.

WuXi: How will Parkinson’s disease treatments evolve over the next five years?

Todd Sherer: A number of new treatments to manage Parkinson’s symptoms are close to market. The U.S. Food and Drug Administration is currently reviewing new drug applications for one treatment for drooling with Parkinson’s disease and two therapies to quickly alleviate motor symptoms when standard medication wears off.

In addition, trials are testing therapies against Parkinson’s genetic targets, such as alpha-synuclein, GBA (glucosylceramidase beta gene), and LRRK2 (leucine rich repeat kinase 2 gene) with potential to slow or stop disease progression. While we still have much to learn about the safety and efficacy of these therapies, we could make significant strides in their development over the next five years.