The Targets to Therapies Initiative systematically identifies and investigates promising but understudied targets for Parkinson’s disease (PD) treatments. It builds on the collected expertise of PD researchers worldwide to accelerate discoveries leading to critically needed therapies.
The Targets to Therapies Initiative builds evidence for promising but understudied therapeutic targets. It focuses on determining and validating whether specific proteins or genes within biological mechanisms involved in PD could serve as effective targets for PD drugs.
Well-known examples of these targets that have therapies already in clinical testing for PD include alpha-synuclein, GBA1 and LRRK2. But many more mechanisms impact the disease and could potentially function as therapeutic targets — if there was sufficient data and clarity to trigger more robust attention from drug developers.
MJFF’s Targets to Therapies Initiative is designed to generate that data and clarity. It employs a groundbreaking collaborative approach that unites fieldwide experts in gathering input on understudied targets and developing a shortlist of those with high potential. Then it funds research teams to mechanistically validate the selected targets for possible future drug development. To further drive progress, all learnings and tools are made freely available through a shared knowledgebase.
An evolution of MJFF’s longstanding focus on translating and validating biology for PD drug development, the initiative was launched in early 2024 by surveying the scientific community to gather input on which targets offer greatest potential for new PD treatments.
Nominated Targets
More than 290 targets were evaluated, and 21 were nominated based on feasibility of addressing bottlenecks over the next two to three years. The Foundation then began convening expert validation teams to study these targets in-depth.
Key to success of the initiative is to leverage the full expertise of our scientific community to inform our efforts related to these targets, whether as a grantee, advisor or collaborator on a target validation team.
Furthermore, while we have started with a shortlist of targets, we continue to gather input on additional targets from experts working on them. To contribute to future target prioritization, we invite nominations for targets to be validated next.
Partnership Opportunities
We are currently collecting information on potential partners, and we look forward to leveraging the full expertise of our scientific community. Complete a short survey to express your interest in working with us on a specific target or targets.
The Targets to Therapies Validation Engine
Three main scientific cores power the Targets to Therapies Initiative: a prioritization and selection core, a validation and toolkit development core, and a public knowledgebase.
Prioritization and Selection
Targets to Therapies assembled the Prioritization and Selection Core — a team of representatives from biotech, pharmaceutical companies, investment firms, and academic and nonprofit research organizations — to develop a framework for prioritizing PD targets and supporting ongoing evaluation of emerging targets.
The initial round focused on selecting targets with potential to slow or modify PD progression. Future efforts will focus on targets that could improve the range of symptoms that occur with PD and impact quality of life.
Validation and Tools
Targets to Therapies aims to generate robust target data profiles and tools to increase confidence in drug development decisions. Preliminary validation plans for the top 21 prioritized targets provide clear starting points for each target’s validation. Efforts are underway to consolidate information on preclinical tools, companies, and key opinion leaders (KOLs) for each target.
The Validation Core — a team of PD biology experts, target validation scientists, and central nervous system drug development specialists — is developing comprehensive data profiles to accelerate target validation. These efforts will address critical gaps, define experimental approaches, and evaluate the feasibility and impact of filling these gaps within a two- to three-year timeframe. In parallel, the Target Toolkit Development Core made up of experts in tool, assay and model development will create preclinical toolkits to support the needs of each target.
These targets stem from efforts across the field, including rich 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).
Public Knowledgebase
The Targets to Therapies Initiative launched a public knowledgebase to make findings on these targets easy to access for researchers and drug developers considering their therapeutic development.
The knowledgebase incorporates high-quality, thoughtfully curated data from target prioritization and validation activities with active involvement from the initiative’s core team of therapeutic and target experts.
Advisors
Scientific Advisory Committee
The Governance Committee, comprised of internal and external stakeholders, provides strategic guidance and feedback, as well as insights to core groups. The committee is designed to ensure target validation efforts align with industry needs and maximize the potential for advancing impactful therapies.
| Targets to Therapies Scientific Advisory Committee | ||
| Stacie Weninger F-Prime Industry & Venture Capitalist KOL | Ekemini Riley Coalition for Aligning Science Program Partner | Todd Sherer MJFF Research Leadership Chief Mission Officer |
| John Dunlop Aliada Therapeutics Industry & Venture Capitalist KOL | Sonya Dumanis Coalition for Aligning Science Program Partner | Brian Fiske MJFF Research Leadership Chief Scientific Officer |
| Adam Knight NeuroVC Industry & Venture Capitalist KOL | Michelle Durborow MJFF Research Leadership SVP, Research Operations | |
Additional advisors are regularly brought in to guide different aspects of the program through committees.
Prioritization and Selection
| Alastair D. Reith, PhD Breckenfield Consulting Limited | Amanda C. Mitchell, PhD Valo Health | Andy Singleton, PhD Global Parkinson’s Genetics Program | Benjamin Logsdon, PhD Cajal Therapeutics, Inc. | Bruce Leuchter, MD Neurvati Neurosciences |
| Cornelis Blauwendraat, PhD Coalition for Aligning Science, Aligning Science Across Parkinson’s, Global Parkinson’s Genetics Program | Darryle Schoepp, PhD Independent | David Stone, PhD ProFound Therapeutics | Elisa Tinelli, PhD Golgi Neurosciences Srl | Fiona Ducotterd, PhD Alzheimer’s Research UK UCL Drug Discovery Institute |
| Jan Stoehr, PhD Abbvie, Neuroscience Discovery | Jessica Sadick, PhD Valo Health | Jonas Hannestad, MD Independent | Jonathan Behr, PhD Dementia Discovery Fund, SV Health Investors | Julie Miller, PhD Depts. of Neuroscience and Speech, Language and Hearing Sciences, University of Arizona |
| Lee Rubin, PhD Dept of Stem Cell and Regenerative Biology, Harvard University | Martin Citron, PhD UCB Biopharma | Matthew Nelson, PhD Genscience LLC | Mina Ryten, PhD UK Dementia Research Institute and Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge | Robin Kleiman, PhD Myrobalan Therapeutics |
| Sarah Silvergleid Schrodinger | Steve Wood, PhD Neuron23, Inc. | Tina Schwabe, PhD | Tom Otis, PhD Lario Therapeutics | Victoria Dardov, PhD Technome |
| Virginie Buggia-Prevot, PhD Valo Health | Alexandra Nelson, MD, PhD UC San Francisco | Anatol C. Kreitzer, PhD MapLight Therapeutics | Andy Singleton, PhD Global Parkinson’s Genetics Program | Carina Oehrn, MD, PhD University of California, Davis |
| Cornelis Blauwendraat, PhD Coalition for Aligning Science, Aligning Science Across Parkinson’s, Global Parkinson’s Genetics Program | Darryle Schoepp, PhD Independent consultant | David G. Standaert, MD, PhD University of Alabama at Birmingham, Heersink School of Medicine | David Stone, PhD ProFound Therapeutics | Julie Miller, PhD University of Arizona |
| Lee Dawson, PhD Cerevance Ltd. | Mark Forman, MD, PhD Ventyx Biosciences | Milton Biagioni, MD UCB Biopharma | Rebekah Evans, MD Georgetown University Medical Center | Robin Kleiman, PhD Myrobalan Therapeutics |
| Sarah Almond, PhD Independent | Sarah Silvergleid Schrodinger | Shelia Fleming, PhD Northeast Ohio Medical University | Stephanie M McTighe McTighe BioScience LLC | Thomas Wichmann, MD Emory University |
| Tom Otis, PhD Lario Therapeutics |
Validation and Tools
Advisors for the Validation Target Team include:
| Alastair Reith, PhD | Breckenfield Consulting Ltd. | Endolysosomal Targets* |
| Anastasia Henry, PhD | Denali Therapeutics | Endolysosomal Targets* |
| Magdalene Moran, PhD | Topo Therapeutics | Endolysosomal Targets* |
| Benjamin Logsdon, PhD | Cajal Therapeutics, Inc. | NOD2 |
| David Rickard, PhD | Independent (formerly GSK) | NOD2 |
| Gabriel Nunez, MD | University of Michigan | NOD2 |
| Ivo Gomperts Boneca, PhD | Institut Pasteur & INSERM | NOD2 |
| Jia Wolfe, PhD | Orchard Therapeutics | NOD2 |
| John Nuss, PhD | Ventyx Biosciences, Inc. | NOD2 |
| Jonathan Behr, PhD | Dementia Discovery Fund, SV Health Investors | NOD2* |
| Lee Dawson, PhD | Cerevance Ltd. | NOD2 |
| Rebecca Senter, PhD | Vertero Therapeutics | NOD2* |
| Stewart Campbell, PhD | Vertero Therapeutics | NOD2 |
| Žiga Jakopin | University of Ljubljana | NOD2 |
| Irit Rappley, PhD | Partner, Other Stuff Strategies | OGA |
| Kalpana Merchant, PhD | TransThera Consulting Co. and Northwestern University | OGA* |
| Paul W Thompson, PhD | Lelantos Bio Ltd. | STING1* |
| Rita Cowell, PhD | University of Alabama at Birmingham | STING1* |
| Christian Mirescu | Independent (formerly GSK) | TLR2 |
| Rebecca Senter, PhD | Vertero Therapeutics | TLR2* |
| *Co-Chair | ||
The network for the Target to Therapies Initiative includes:
Learn More
- In-depth Description of the Targets to Therapies Initiative in npj Parkinson's Disease
- Targets to Therapies: A New Target De-Risking Initiative at MJFF
- MJFF Target Prioritization Initiative: Latest Updates and Spring 2024 Survey Outcomes
What You Can Do
Express interest in a target on our list: Researchers with an interest in working with us on a specific target can complete a short Target Interest Form. MJFF research staff will evaluate submitted interest forms and, when there is a fit, reach out for additional information.
Nominate another target: If you have a target that we should know about, please complete this form.
Apply for access to the Public Knowledgebase: Complete the Access Request form.
Ask a question about the program: If you have a question about the Targets to Therapies Initiative, please send an email to targets2therapies@michaeljfox.org.