The Michael J. Fox Foundation and The Silverstein Foundation for Parkinson's with GBA Grant Nearly $3 Million to Studies into Disease's Most Common Known Genetic Contributor
NEW YORK, Feb. 20, 2019 /PRNewswire/ -- The Michael J. Fox Foundation for Parkinson's Research (MJFF) and The Silverstein Foundation for Parkinson's with GBA announce nearly $3 million in grants to studies investigating glucocerebrosidase beta acid (GBA). Mutations in the GBA gene are the most common genetic risk factors for Parkinson's, affecting about 10 percent of the more than 6 million people estimated to have the disease. The projects selected through this joint funding program aim to better understand the effect of GBA mutations -- and the role of GBA more generally -- and advance treatments against this target.
"Defining the GBA pathway and its role in disease, including in patients without a GBA mutation, could point to new therapeutic approaches that may slow or stop Parkinson's," said MJFF CEO Todd Sherer, PhD. "This partnership with the Silverstein Foundation streamlined the grant process to more quickly direct funding to these promising projects, speeding their efforts to help Parkinson's patients."
Silverstein Foundation Founder Jonathan Silverstein said, "We are very pleased with the collaboration with The Michael J. Fox Foundation and feel confident that the projects chosen will significantly add to the library of knowledge around GBA and propel new treatments for people living with Parkinson's and, perhaps, individuals at risk for the disease."
Previous research found that GBA mutations hamper activity of the glucocerebrosidase (GCase) enzyme, a member of the cell's cleaning crew that degrades damaged or excess cell parts. Build-up of cell parts (e.g., lipids and cellular proteins) can be toxic, resulting in the cell damage seen in Parkinson's disease. While linked directly to GBA gene mutations, GCase inhibition is also found in Parkinson's patients without these mutations. Therefore, therapies to heighten the enzyme's activities or mimic its effects may help a wider Parkinson's patient base. Three such medications are already in clinical trials.
From the 92 proposals submitted, MJFF and the Silverstein Foundation have selected 16 of the most promising projects to support through their joint funding program. Descriptions of the programs follow.
GBA Biology
These projects aim to define novel biomarker candidates or therapeutic targets by investigating the role of GCase and impact of GBA mutations.
-- Two projects are looking for other genetic factors that influence
Parkinson's risk with a GBA mutation. Tim Ahfeldt, PhD, at the Icahn
School of Medicine at Mount Sinai is using gene-editing (CRISPR)
technologies to modulate the expression of GBA and other genes in an
effort to identify other risk factors. Justin Martin O'Sullivan, PhD, at
the University of Auckland will use computer programs to identify genes
controlled by the DNA switches in the GBA gene and then investigate how
these switches affect cells and contribute to Parkinson's disease.
-- Grantees are using other cutting-edge technology to investigate the
cellular effects of GBA mutations. Ricardo Feldman, PhD, at the
University of Maryland, Baltimore is using induced pluripotent stem
cells to examine the cellular effects of GBA mutations and to test if
reversing some of those effects can protect dopamine cells. Anthony
Futerman, PhD, at the Weizmann Institute of Science in Israel is
applying advanced RNA sequencing and proteomics analysis to brain tissue
samples from people with idiopathic Parkinson's, those with
GBA-associated Parkinson's and control volunteers to identify
GBA-specific pathology.
-- The immune system is a growing area of interest in Parkinson's research.
Manoj Kumar Pandey, PhD, at the Cincinnati Children's Hospital Medical
Center is studying how GBA mutations may lead to inflammation, which is
also seen in Parkinson's disease, and Michel Desjardins, PhD, at the
Université de Montréal is studying the role of GCase in autoimmune
mechanisms after observing that GCase expression in immune cells
influences this response.
-- Emily M. Rocha, PhD, and J. Timothy Greenamyre, MD, PhD, at the
University of Pittsburgh will work to connect deficits in GCase with
another leading genetic target: LRRK2. This work could explore the
potential of LRRK2 inhibitors (currently in clinical trials) for a
broader Parkinson's population.
-- Three projects are investigating other cellular players in the GBA
pathway, which may be potential therapeutic targets. Aarnoud Cornelis
van der Spoel, PhD, at Canada's Dalhousie University is investigating a
class of cellular fats called sphingolipids that are impacted by GBA
mutations. Peter Vangheluwe, PhD, at Belgium's KU Leuven research
university is looking at a transporter of the lipid glucosylceramide,
which builds up in response to GBA mutations. And Friederike Zunke, PhD,
at the University of Keil in Germany is looking for the site of
interaction between GCase and the protein LIMP-2, which transports GCase
to the lysosome.
GBA Biomarkers
Two projects are looking for objective measures that could help in patient care and in research, by aiding in subject selection and therapeutic impact assessment.
-- David Eidelberg, MD, at the Feinstein Institute for Medical Research
will follow Parkinson's patients with and without GBA mutations over 18
months to assess progression as measured through clinical examinations
and MRI scans in an effort to develop an imaging biomarker.
-- Michele Matarazzo, MD, at the University of British Columbia is looking
for predictive biomarkers. Mutation carriers with PD and without the
disease will undergo clinical evaluations, blood tests, and MRI and PET
scans.
GBA Therapies
Grantees are taking varied approaches to correct or counteract the effects of lower GCase activity.
-- Three grantees are testing compounds against GCase. David Vocadlo, PhD,
at Simon Fraser University is rapidly screening thousands of compounds
to identify those that can increase GCase and testing leads in
Parkinson's models. Marlene Jacobson, PhD, at Temple University is
testing compounds to improve lysosomal function and increase GCase
levels in fibroblasts from Parkinson's patients with GBA mutations.
Marta Martinez-Vicente, PhD, at Vall d'Hebron Research Institute in
Barcelona is conducting pre-clinical tests of drug compounds from Gain
Therapeutics that aim to stabilize GCase and recover its activity.
-- Magdalene Moran, PhD, at Rheostat Therapeutics is looking at another
target, testing activators of TRPML1. Experiments showed activation of
this ion channel can fix lysosomal malfunctions, which are associated
with GBA mutations.
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 more information, visit www.michaeljfox.org.
About The Silverstein Foundation for Parkinson's with GBA
The Silverstein Foundation is a 501(c)(3) non-profit organization focused on investing in cutting-edge therapeutic approaches for the treatment and prevention of Parkinson's disease in glucocerebrosidase (GBA) mutation carriers. The Foundation collaborates with clinicians, scientists, and biotechnology companies to accelerate research and clinical trials in an effort to rapidly bring new disease-modifying therapeutic options to patients. Under the leadership of a world-class team with strong domain expertise across neurodegenerative diseases, drug formulation chemistry, translational research, and drug development and commercialization, the Foundation has funded over 30 projects across seven different therapeutic approaches since its inception in 2017. The Foundation applies a unique flexible funding model including both new company formation and traditional research grants to deliver in real-time on its mission of rapidly developing novel disease-modifying treatments for Parkinson's disease.
For more information, visit www.silversteinfoundation.org.
SOURCE The Michael J. Fox Foundation for Parkinson's Research
