A community-led initiative to de-risk and advance Parkinson's disease therapeutic targets

Alexandra Vaiana¹, Jonathan Behr^{2

3}, Ryan Birol¹, Cornelis Blauwendraat⁴, Bradford Casey¹, Kushan Chowdhury⁵, Martin Citron⁶, Joshua Crapser⁷, Victoria Dardov⁸, Fiona Ducotterd⁹, Sonya Dumanis⁴, John Dunlop¹⁰, Michelle Durborow¹, Brian Fiske¹, Jessica Golden¹, Jonas Hannestad¹¹, Wendy Hung¹², Jennifer Kemp¹³, Robin Kleiman¹⁴, Adam Knight¹⁵, Andrew Koemeter-Cox¹, Bruce Leuchter¹⁶, Bejamin A Logsdon¹⁷, Rita Marreiros¹⁸, Julie E Miller¹⁹, Amanda Mitchell²⁰, Pooja Mukherjee²¹, Grace Navarro¹, Matthew R Nelson^{22

23}, Karoly Nikolich²⁴, Tom Otis²⁵, Nicole Polinski¹, Shima Rastegar-Pouyani²⁶, Alastair D Reith²⁷, Ekemini Riley⁴, Lee Rubin²⁸, Mina Ryten^{29

30}, Jessica Sadick³¹, Tina Schwabe³², Todd Sherer¹, Sarah Silvergleid³³, Andrew Singleton³⁴, Lara St Clair¹, Jan Stoehr³⁵, David J Stone³⁵, Julianna Sullivan¹, Nicole Tanenbaum³⁶, Elisa Tinelli³⁷, Kate Trimble¹, Yifei Wang³⁸, Stacie Weninger³⁹, Nicolás Wiggenhauser⁴⁰, Stephen Wood⁴¹, Darryle Schoepp⁴², Virginie Buggia-Prevot³¹, Shalini Padmanabhan¹, Gaia Skibinski⁴³

Affiliations

¹ The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
² SV Health Investors, Boston, MA, USA.
³ Dementia Discovery Fund, Boston, MA, USA.
⁴ Coalition for Aligning Science, Chevy Chase, MD, USA.
⁵ Biotech Connection Bay Area, San Francisco, CA, USA.
⁶ UCB Pharma, Brussels, Belgium.
⁷ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Technome, Herndon, VA, USA.
⁹ University College London, Great Britain, UK.
¹⁰ Aliada Therapeutics, Boston, MA, USA.
¹¹ Gain Therapeutics, Bethesda, MD, USA.
¹² University of California, San Franscisco, San Franscisco, CA, USA.
¹³ Strategies for Open Science (Stratos), Santa Cruz, CA, USA.
¹⁴ Myrobalan Therapeutics, Medford, MA, USA.
¹⁵ Neuro.VC, San Franscisco, CA, USA.
¹⁶ Neurvati Neurosciences, New York, NY, USA.
¹⁷ Cajal Neuroscience Inc., Seattle, WA, USA.
¹⁸ Chan Zuckerberg Biohub, San Franscisco, CA, USA.
¹⁹ Departments of Neuroscience and Speech, Language and Hearing Sciences, University of Arizona, Tucson, AZ, USA.
²⁰ Independent Consultant, Seattle, WA, USA.
²¹ University of California Berkeley, Department of Molecular and Cell Biology, Berkeley, CA, USA.
²² Genscience LLC, New York, NY, USA.
²³ Deerfield Management, New York City, NY, USA.
²⁴ Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA.
²⁵ Lario Therapeutics Ltd., Edinburgh, Scotland, UK.
²⁶ Memory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁷ Breckenfield Consulting Ltd., London, UK.
²⁸ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
²⁹ UK Dementia Research Institute and Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
³⁰ Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
³¹ Valo Health Inc., Lexington, MA, USA.
³² Nine Square Therapeutics, South San Franscisco, CA, USA.
³³ Schrödinger Inc., New York, NY, USA.
³⁴ Global Parkinson's Genetics Program, Chevy Chase, MD, USA.
³⁵ AbbVie, Cambridge, MA, USA.
³⁶ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
³⁷ Golgi Neurosciences S.r.l, Milan, Italy.
³⁸ Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
³⁹ F-Prime Capital Partners, Boston, MA, USA.
⁴⁰ Interdepartmental Doctoral Program in Anthropological Sciences, Stony Brook University, Stony Brook, NY, USA.
⁴¹ Neuron23 Inc., South San Franscisco, CA, USA.
⁴² Independent Pharmaceutical Research Consultant, Ardmore, PA, USA.
⁴³ The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA. gskibinski@michaeljfox.org.

PMID: 40541945
PMCID: PMC12181325
DOI: 10.1038/s41531-025-01039-3

Review

A community-led initiative to de-risk and advance Parkinson's disease therapeutic targets

Alexandra Vaiana et al. NPJ Parkinsons Dis. 2025.

. 2025 Jun 20;11(1):179.

doi: 10.1038/s41531-025-01039-3.

Authors

Affiliations

¹ The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
² SV Health Investors, Boston, MA, USA.
³ Dementia Discovery Fund, Boston, MA, USA.
⁴ Coalition for Aligning Science, Chevy Chase, MD, USA.
⁵ Biotech Connection Bay Area, San Francisco, CA, USA.
⁶ UCB Pharma, Brussels, Belgium.
⁷ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Technome, Herndon, VA, USA.
⁹ University College London, Great Britain, UK.
¹⁰ Aliada Therapeutics, Boston, MA, USA.
¹¹ Gain Therapeutics, Bethesda, MD, USA.
¹² University of California, San Franscisco, San Franscisco, CA, USA.
¹³ Strategies for Open Science (Stratos), Santa Cruz, CA, USA.
¹⁴ Myrobalan Therapeutics, Medford, MA, USA.
¹⁵ Neuro.VC, San Franscisco, CA, USA.
¹⁶ Neurvati Neurosciences, New York, NY, USA.
¹⁷ Cajal Neuroscience Inc., Seattle, WA, USA.
¹⁸ Chan Zuckerberg Biohub, San Franscisco, CA, USA.
¹⁹ Departments of Neuroscience and Speech, Language and Hearing Sciences, University of Arizona, Tucson, AZ, USA.
²⁰ Independent Consultant, Seattle, WA, USA.
²¹ University of California Berkeley, Department of Molecular and Cell Biology, Berkeley, CA, USA.
²² Genscience LLC, New York, NY, USA.
²³ Deerfield Management, New York City, NY, USA.
²⁴ Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA.
²⁵ Lario Therapeutics Ltd., Edinburgh, Scotland, UK.
²⁶ Memory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁷ Breckenfield Consulting Ltd., London, UK.
²⁸ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
²⁹ UK Dementia Research Institute and Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
³⁰ Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
³¹ Valo Health Inc., Lexington, MA, USA.
³² Nine Square Therapeutics, South San Franscisco, CA, USA.
³³ Schrödinger Inc., New York, NY, USA.
³⁴ Global Parkinson's Genetics Program, Chevy Chase, MD, USA.
³⁵ AbbVie, Cambridge, MA, USA.
³⁶ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
³⁷ Golgi Neurosciences S.r.l, Milan, Italy.
³⁸ Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
³⁹ F-Prime Capital Partners, Boston, MA, USA.
⁴⁰ Interdepartmental Doctoral Program in Anthropological Sciences, Stony Brook University, Stony Brook, NY, USA.
⁴¹ Neuron23 Inc., South San Franscisco, CA, USA.
⁴² Independent Pharmaceutical Research Consultant, Ardmore, PA, USA.
⁴³ The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA. gskibinski@michaeljfox.org.

PMID: 40541945
PMCID: PMC12181325
DOI: 10.1038/s41531-025-01039-3

Abstract

Identifying effective therapeutic targets for Parkinson's disease (PD) is challenging, with no current disease-modifying therapies available. To address this, The Michael J. Fox Foundation for Parkinson's Research launched the Targets to Therapies (T2T) initiative, uniting experts to prioritize and validate promising targets. T2T aims to develop validation strategies, create comprehensive target data profiles, and build tools to support drug development, ultimately accelerating the discovery of new therapies for PD patients.

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Conflict of interest statement

Competing interests: The authors entered into an agreement to represent themselves, and not their affiliated institutes throughout the Prioritization and Selection process. However, the authors declare the following potential or perceived conflicts of interest which could bias their thoughts on the targets, either consciously or subconsciously: J.B. is an employee of SV Health Investors, M.C. is an employee of UCB Pharma and has access to stock options of UCB, V.D. is an employee of Technome, J.D. is an employee of Alaida Therapeutics, J.H. is an employee of Gain Therapeutics, R.K. is an employee of Myrobalan Therapeutics, A.K. is the Founder and a shareholder of Neuron23, he is affiliated with Neuro.VC, which is an investor in Vanqua Bio, Neuron23, and Capsida Biotherapeutics, B.L. is the CEO of Neurvati Neurosciences, a company focused on in-licensing clinical-stage molecules across the neuroscience landscape, not currently active in PD/neurodegenerative disease but could engage around opportunities in this space in the future, B.A.L. is an employee of Cajal Neuroscience, M.R.N. is an employee of Deerfield Management and Genscience LLC., T.O. is an employee of Lario Therapeutics, which works on CACNA1E and CACNA1D targets, J. Sadick and V.B.P. are employed by and have equity in Valo Health, a company engaged in various drug discovery and development projects, including certain neuroimmunology targets, T. Schwabe is an employee of Nine Square Therapeutics and currently works on the Trpml1 target, which was selected on the shortlist of targets for further evaluation, S.S. is an employee of Schrodinger, Inc., J. Stoehr and D.J.S. are employees of AbbVie Inc., E.T. is an employee of Golgi Neurosciences, working on TREM2, MCOLN1 and CACNA1D, S. Weninger is an employee of F-Prime and sits on the boards of Tenvie and Atalanta, S. Wood is an employee and stockholder of Neuron23, Inc. A.D.R., D.S., and A.M. are active consultants in the biopharmaceutical space. The remaining authors declare no financial competing interests: A.V., R.B., C.B., B.C., K.C., J.C., F.D., S.D., M.D., B.F., J.G.,W.H., J.K., A.K.C., R.M., J.E.M., P.M., G.N., K.N., N.P., S.R.P., E.R., L.R., M.R., T. Sherer, A.S., L.S., J. Sullivan, N.T., K.T., Y.W., N.W., S.P., G.S.

Figures

**Fig. 1. The engine driving T2T comprises three interconnected cores.**
Target Prioritization and Selection, Target Validation and Toolkit Development, and the Target Knowledge Base. The outcomes of this approach will be comprehensive target data packages that are well-positioned for therapeutic development and an informed community of researchers and investors with expertise on these targets, facilitating partnerships and potential investments to advance therapeutic development.

**Fig. 2. Milestones and timeline for prioritization and selection.**
Over a 9-month period, 290 targets were evaluated and prioritized through a staged approach involving multiple rounds of diligence. This process included the creation of target scorecards, heatmaps, and target profile summaries, which were used in successive rounds of evaluation to refine the list to 21 priority targets for initial de-risking validation efforts.

**Fig. 3. Summary of nominated targets and target list composition.**
A A total 210 targets were nominated, of which 71 overlapped with MJFF-funded targets, while 139 were new nominations. B Nominations were received from a diverse group of 227 stakeholders across various sectors. C The comprehensive list of 290 targets includes both disease-modifying and symptomatic targets. D Targets span different phases of the discovery pipeline, classified as: group I (no tool compounds available), group II (preclinical tool compounds available), and group III (drugs already in clinical studies for CNS or non-CNS indications).

**Fig. 4. Scorecard categories enabled compiling of data diligence on the targets.**
The “light scorecard” categories were used in the initial round of prioritization and selection, while the “deep scorecard” expanded on these, providing additional diligence in each category for a more thorough evaluation of each target.

**Fig. 5. Target profile summaries and knowledge base “illuminate”.**
A–C These represent one of the 59 target profile summaries created for the prioritized targets. A, B The first two slides summarize target diligence across scorecard categories such as therapeutic mechanism of action (MOA), efficacy evidence in preclinical PD models, patient biology, and therapeutic potential. C The third slide provides a summary of each key diligence area, along with a list of gaps in the target profile and associated risks in therapeutic development for the target. D A screenshot of the target profile page in the knowledge base displays the data collected during this round of prioritization and selection.

**Fig. 6. Next steps for T2T.**
An outline of the immediate actions for T2T, including target prioritization and selection, target validation, and the development of the knowledge base.

See this image and copyright information in PMC

References

1. Dorsey, E. R., Sherer, T., Okun, M. S. & Bloem, B. R. The emerging evidence of the Parkinson pandemic. J. Parkinsons Dis.8, S3–S8 (2018). - PMC - PubMed
1. Tolosa, E., Marti, M. J., Valldeoriola, F. & Molinuevo, J. L. History of levodopa and dopamine agonists in Parkinson’s disease treatment. Neurology50, S2–10 (1998). - PubMed
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1. Schorken, Z., Klapper, K. & Fiske, B. Parkinson’s priority therapeutic clinical pipeline report (The Michael J. Fox Foundation for Parkinson’s Research, Zenodo, 2023).

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A community-led initiative to de-risk and advance Parkinson's disease therapeutic targets

Affiliations

A community-led initiative to de-risk and advance Parkinson's disease therapeutic targets

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources