MJFF awards grants to advance 5 new targets for Parkinson’s drugs
Funding goes to potential treatments investigating genes, proteins
Three research teams investigating five high-potential targets for new Parkinson’s disease therapies received initial funding under a multi-year initiative from the Michael J. Fox Foundation for Parkinson’s Research (MJFF).
The grants are the first to be awarded under MJFF’s Targets to Therapies Initiative, which aims to advance the validation of new biological targets for treatments. Over the past two years, MJFF has evaluated more than 280 targets and selected 21 priority targets and their pathways, which will now advance toward validation efforts.
The five targets — the NOD2, TMEM175, and ATP13A2 genes and the TRPML1 and OGA proteins — address underlying disease mechanisms in Parkinson’s, including the clearance of toxic proteins, the maintenance of cellular recycling, and the regulation of inflammatory activity.
“Our mission is to widen the path toward new treatments for people living with Parkinson’s,” Gaia Skibinski, PhD, director of translational therapeutics at MJFF, said in a foundation press release. “By moving from identifying promising targets to actively validating them, we’re beginning to build the evidence needed to expand the number of well-characterized, druggable opportunities in the [Parkinson’s] pipeline.”
Targets to Therapies focuses on identifying and validating whether specific genes and proteins involved in Parkinson’s biological mechanisms can be used as targets for developing treatments for the disease.
Targeting targets
Well-known targets include alpha-synuclein, the protein that forms toxic clumps inside nerve cells contributing to their death, and the GBA1and LRRK2 genes, mutations in which are the most common genetic causes of Parkinson’s. Ongoing trials are testing drugs for these targets, according to MJFF.
MJFF researchers identified the new targets in collaboration with programs supported by Aligning Science Across Parkinson’s. These include the Collaborative Research Network, the Parkinson’s Progression Markers Initiative, and the Global Parkinson’s Genetics Program.
In Parkinson’s, the NOD2 gene may be abnormally activated by alpha-synuclein, triggering inflammatory responses that contribute to neuronal death. Reducing NOD2 activity could help limit inflammation and protect neurons.
Dysfunction of the TMEM175 gene can impair the cell’s waste-disposal and recycling systems. Activating TMEM175 may restore these pathways, enhancing the breakdown of toxic alpha-synuclein aggregates. A comparable protective effect is observed with ATP13A2, a gene linked to rare cases of early-onset Parkinson’s, where increased activity supports cellular clearance mechanisms.
The TRPML protein forms ion channels on cellular membranes that facilitate the removal of alpha-synuclein clumps from cells. In contrast, inhibiting the OGA protein may reduce alpha-synuclein accumulation by limiting processes that promote its buildup.
“So far, $7.5 million has been awarded to these target validation projects plus generation of cross-target research tools, with up to an additional $11.5 million expected to be committed,” MJFF said. “Additional rounds of funding are scheduled for 2026 and 2027.”
MJFF said it’s also releasing the first public set of evidence gaps and proposed validation approaches for about 59 high-potential targets. These targets will be available through the T2T Target Explorer platform, a digital open resource that joins evidence, expert assessments, and validation plans for each target.
“This kind of coordinated, field-wide effort is exactly what’s needed to unlock the next generation of Parkinson’s therapeutics,” said Stacie Weninger, PhD, a venture partner with F-Prime Capital and member of the T2T steering committee. “By bringing together experts across industry and academia and making data openly accessible, MJFF is helping de-risk early target biology so developers can pursue the most promising opportunities with confidence.”
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