The Michael J. Fox Foundation Convenes Global Experts and Launches Initiative to Speed Study of Druggable Targets for Parkinson's Disease

• Targets to Therapies Initiative will de-risk drug development to expand foundational knowledge of underexplored drug targets through a multi-year research program
• Research community-driven survey deployed by The Michael J. Fox Foundation identified several hundred diverse promising targets for drug development in Parkinson's disease
• Consortium of Parkinson's scientists, industry researchers and investors narrowed down list of promising candidates and now prioritize five targets for immediate exploration, with an additional seven entering the pipeline for the next round of study

NEW YORK, March 25, 2025 /PRNewswire/ -- Today, The Michael J. Fox Foundation for Parkinson's Research (MJFF) announces the selection of five high priority targets through its Targets to Therapies Initiative — a program aimed at expanding the number of promising, druggable biological targets within the Parkinson's disease (PD) pipeline. MJFF's Targets to Therapies Initiative is convening an international group of experts from industry, academia and the clinic to plot the course of work needed to bridge initial identification of these targets with the rigorous evidence needed to support launching new therapeutic development. The program represents a next-step evolution of the Foundation's long-standing commitment to supporting early-stage translational research and a more robust PD treatment pipeline.

In Parkinson's there are already several well-characterized drug targets — biology that can be specifically homed in on for treatment — including alpha-synuclein, the protein most closely associated with PD, as well as LRRK2 and GBA1, proteins with strong genetic ties to the disease. However, there remains a pressing need to assess the many new biological targets to see which may be most viable for addressing symptoms and slowing disease. The initiative will invest tens of millions of dollars to expand the field's knowledge of underexplored targets and make it less risky for drug developers to invest in therapies which leverage that knowledge.

"The Michael J. Fox Foundation exists to increase the number of available treatments for people and families with Parkinson's. Expanding the number of well-characterized, druggable targets is an important step in that direction," said Shalini Padmanabhan, PhD, senior vice president of discovery and translational research at MJFF. "Ultimately, the knowledge gives us a field-wide view of emerging targets so that we can prioritize those that give us the best chance at new therapies."

While MJFF has funded novel target research since its earliest days, to keep pace with an ever-growing wave of biological insight emerging from largescale genetic and biological discoveries, MJFF started the new Targets to Therapies Initiative process in early 2024, surveying the scientific community for input on targets with potential for PD therapeutics. These initial surveys generated a list of more than 280 targets, stemming from efforts across the field, including rich target inputs from MJFF research program datasets and collaboration with the Aligning Science Across Parkinson's (ASAP) initiative-supported programs including the Collaborative Research Network (CRN), the Parkinson's Progression Markers Initiative (PPMI) and the Global Parkinson's Genetics Program (GP2). MJFF consulted with leaders in the PD field, including drug discovery and biotech investment, to narrow that list of potential targets to more than a dozen most promising options, and the Foundation is now convening groups of experts to study these targets in-depth.

Since the Foundation's earliest days, its set out to make as many strategic investments as possible to help drug developers validate new findings in Parkinson's biology and enable novel therapeutic approaches. Over the years, MJFF has developed a sophisticated approach in providing researchers and biopharma with the funding, tools and collaborative partnerships they need. This de-risking strategy has already contributed to major steps forward in catalyzing significant investments in the de-risking of leading genes and their proteins including LRRK2 and alpha-synuclein. Through the Foundation's initiatives, major advances like establishing a collaborative network of labs and industry working on LRRK2 and investing in better defining and measuring the disease through imaging and biomarker tests on alpha synuclein, dozens of therapies are now actively being tested in these pathways, which may lead to slowing or stopping disease progression.

"It's not just about finding druggable targets. It's about finding the most promising druggable targets. We are looking to make advances that lead to new therapies. With the collective might of the scientific community, we can achieve that goal," said Stacie Weninger, PhD, who sits on the Targets to Therapies Initiative governance committee and is the President of FBRI and a Venture Partner at F-Prime. "That's what The Michael J. Fox Foundation has done here—assemble many of the best minds in PD research around the pressing need for new ways to treat Parkinson's."

The five initial targets beginning validation in 2025 include, spanning diverse pathways and stages in the discovery pipeline:

• TMEM175. Dysfunction in TMEM175 can impact cell's waste disposal systems, leading to buildup of toxic substances in neurons.
• ATP13A2. Mutations in ATP13A2 are a rare cause of young-onset Parkinson's disease.
• MCOLN1/TRPML1. Activating TRPML1 may help with clearance of alpha-synuclein, the protein that is linked to Parkinson's when it misfolds.
• OGA. Inhibiting the OGA protein may prevent the degeneration of dopamine neurons, a key contributor to Parkinson's symptoms.
• NOD2. Blocking interaction between NOD2 and alpha-synuclein may reduce neuroinflammation and protect dopamine neurons.

Beginning today MJFF will convene global teams of leaders in the field for the first of five townhalls on the priority targets, with the others following shortly. The teams will start the process of identifying projects that can increase the field's knowledge and make investments in these targets more attractive.

Seven additional targets have also been identified for a second wave of support, and data collection has begun through surveys to the scientific community. Interested scientists can find the surveys here.

The Targets to Therapies Initiative plans to launch a public knowledge base by the end of 2025, making findings on the targets studied easy to access for drug developers and researchers worldwide who may be working on therapeutic development.

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

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 $2 billion 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; creates a robust open- access data set and biosample library to speed scientific breakthroughs and treatment with its landmark clinical study, PPMI; 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 us at www.michaeljfox.org, Facebook, Instagram and LinkedIn. 

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