Objective:
The Targets to Therapies Initiative aims to expand the number of promising, druggable biological targets within the Parkinson’s disease (PD) translational pipeline. Leveraging The Michael J. Fox Foundation’s (MJFF) many years of experience supporting target validation and advancement, the initiative takes a fresh approach combining community-sourced target nomination with expert panel-guided prioritization and validation roadmaps to deliver targets that are ripe for Parkinson’s therapeutic development.
Program Details:
Genetic and biological studies have linked many potential cellular pathways and targets to PD pathogenesis. Some of these targets have advanced far into the PD drug development pipeline, including targets such as alpha-synuclein and LRRK2. However, many additional promising targets lack sufficient data and clarity to trigger robust therapeutic attention.
To serve this need, MJFF's Target to Therapies Initiative will expand and mechanistically validate promising, druggable targets in the field of Parkinson's disease by identifying a shortlist of priority targets for dedicated de-risking focus over the next three -to -four years. MJFF started this process in early 2024, surveying the scientific community through a Request for Information (RFI), seeking input on targets with potential for Parkinson's disease (PD) therapeutics. These initial surveys generated a list of more than 280 targets. MJFF consulted with leaders across the PD field to narrow that list to five of the most promising options, and in March 2025, the Foundation began convening groups of experts to study these targets in-depth.
| 227 Total Responders to RFI | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Academia | Industry | Clinical | VC/Investor | Consultant | Non-Profit | Government | |||||||||||||
| 116 | 113 | 11 | 3 | 1 | 2 | 5 | |||||||||||||
“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." - Shalini Padmanabhan, PhD, senior vice president of discovery and translational research
The five initial targets beginning validation in 2025 span 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.
Seven additional targets have also been identified for a second wave of support.
The initiative will develop de-risking roadmaps for these prioritized targets, identifying key expertise and critical resource needs to support their advancement. These roadmaps may leverage a variety of approaches, including community funding calls, tool and resource development and/or coordinated, MJFF-led activities. The T2T engine brings in targets and prioritizes the most promising for further exploration.
The T2T program plans to launch a public knowledge base, making findings on these targets easy to access for drug developers who may be considering therapeutic development.
This initiative will reduce the risk of biotech and pharmaceutical investment in exploring new treatment opportunities in the field of Parkinson's disease.
To Learn More:
Targets to Therapies: A New Target De-Risking Initiative at MJFF
MJFF Target Prioritization Initiative: Latest Updates and Spring 2024 Survey Outcomes
If you have questions about the program or are interested in nominating a target or contributing to the initiative, please email: targets2therapies@michaeljfox.org