The Michael J. Fox Foundation Funds Three Research Teams to Seek Common Biological Pathways Underpinning Environment, Genetics and Aging in Parkinson's Onset and Progression

NEW YORK, March 22, 2018 /PRNewswire-USNewswire/ -- As part of its mission to accelerate the development of urgently needed treatment breakthroughs for Parkinson's disease (PD), The Michael J. Fox Foundation for Parkinson's Research (MJFF) announces a program investigating the pathogenesis of Parkinson's: PATH to PD. This ambitious multi-team, multi-million-dollar initiative aims to identify molecular/cellular events that may play a role in Parkinson's onset and progression, whether in the presence of environmental exposures, genetic factors and aging.

"The vast diversity of pathways implicated in Parkinson's pathology to date indicates that multiple physiological routes can lead to PD, and these routes may intersect or be temporally dependent," said Todd Sherer, PhD, MJFF CEO. "Through PATH to PD, our Foundation aims to encourage researchers to bring a holistic new approach to bear on refining today's understanding of what Parkinson's is — so that we can better strategize how to slow or stop the disease."

A Holistic Approach

Parkinson's arises from multiple, complicated gene-environment interactions on the poorly understood background of aging. The past two decades have brought substantial growth in understanding of the disease, in particular a strong appreciation of the role of genetics and the cellular pathways they influence. The emerging research picture of Parkinson's is that of a vast, interwoven network culminating in a disease with great variability in cause, rates of progression, symptomology and treatment responses.

Each PATH to PD-funded research team will receive $2 million over two years to holistically investigate genetics, environment and aging, the most important known contributors to Parkinson's disease. Teams will look for a common framework that links mechanisms through which these risk and causal factors may lead to Parkinson's — independently and/or in concert with each other. Teams additionally will work to understand whether disease mechanisms at play in idiopathic forms of PD hew more closely to those seen in the presence of genetic abnormalities or environmental exposures.

• Environmental and Genetic Mechanisms of Parkinson's will seek out links between environmental and genetic triggers of disease. This project will investigate the mechanisms through which neurotoxins cause neurodegeneration and how these pathways interact with known genetic factors such as LRRK2, a leading genetic cause of PD.
  
  "It is an honor to be selected by The Michael J. Fox Foundation to participate in this unique collaborative project. Our work focuses on the commonalities of Parkinson's disease causation, whether it's due to genetic mutations or environmental exposures. We hope that by defining these common mechanisms, we will know how best to intervene therapeutically to slow or stop disease progression," said Principal Investigator J. Timothy Greenamyre, MD, PhD, of the Pittsburgh Institute for Neurodegenerative Diseases and the University of Pittsburgh.
  
  
• Foundational Data Initiative: Mapping Genetic Effects in Parkinson's will grow nerve cells from induced pluripotent stem cells and use advanced "omics" techniques (e.g., genomics, proteomics, metabolomics) to map how various genetic changes lead to cellular and molecular changes associated with PD.
  
  "We are pleased to be part of a truly multidisciplinary group that brings together experts with a common goal to produce foundational data that will accelerate the field's ability to understand the disease processes and to find logical places for intervention," said Principal Investigator Andrew Singleton, PhD, of the National Institute on Aging, part of the National Institutes of Health.
  
  
• Aging and Parkinson's Disease will investigate how cellular aging and related DNA and mitochondrial damage contributes to neurodegeneration. Advanced gene-editing techniques will allow this team to investigate these processes in both rodent and human cells.
  
  "I'm honored and extremely grateful to MJFF for this award. It gives us the opportunity to do the kind of innovative, interdisciplinary science that can lead to conceptual breakthroughs and identification of the shortest possible path to a real strategy for stopping Parkinson's disease," said Principal Investigator D. James Surmeier, PhD, of Northwestern University.

A Complex Disease

While the Parkinson's drug development pipeline is brimming with greater activity than ever before, many unmet medical needs persist in the treatment and management of Parkinson's disease. The greatest of these remains the need for a so-called "disease-modifying" treatment, or one that could slow or stop the underlying progression of Parkinson's disease. This is something no currently available treatment has been proven to do.

Researchers believe a disease-modifying treatment has the best chance for success if it targets key underlying pathogenic pathways implicated in the disease. 

Several dozen different gene mutations have been linked to inherited, familial PD, but the vast number of PD cases occur with no known gene mutation. The different genes linked to familial PD thus far lie in multiple, distinct pathways, including protein balance/recycling, cellular energy metabolism, stress response, neurotransmission and inflammation/immune function, among others.

Environmental factors associated with heightened risk of PD include previous head injury, heavy metal exposure, pesticide exposure and previous brain infection.

Above all, aging is the single greatest risk factor for PD, which implicates either physiological changes that occur naturally with advanced age or a lifetime accumulation of otherwise minor environmental exposures that either themselves accumulate and eventually lead to development of PD or contribute to "turn on" PD risk genes — or a combination of both.

"With Parkinson's prevalence expected to double by 2040 to nearly 13 million people worldwide, our Foundation believes it is our obligation to continue building on current research momentum to eradicate this disease once and for all," concludes CEO Sherer. "We are grateful to our supporters, many living with Parkinson's disease, whose generosity enables us to drive innovation toward breakthroughs through programs like PATH to PD."

About The Michael J. Fox Foundation for Parkinson's Research

As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $800 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.

For current funding opportunities, visit www.michaeljfox.org/funding.

SOURCE The Michael J. Fox Foundation

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