Advancing Development of LRRK2-Targeted Therapeutics for Parkinson's Disease: Conference Proceedings and Roadmap for Research.

Abstract

In June 2025, the Michael J. Fox Foundation for Parkinson's Research (MJFF) hosted an in-person workshop, LRRK2-Targeted Therapeutics Roundtable: Advancing Clinical Development for Parkinson's Disease, convening researchers, clinicians, industry representatives, and funders to discuss opportunities for communication, coordination, and collaboration to advance the development of therapeutics that target leucine-rich repeat kinase 2 (LRRK2). The purpose of this multistakeholder workshop was to create a collaborative platform for researchers, clinicians, industry representatives, and funders to discuss the trade-offs and opportunities in using various clinical trial strategies, including trade-offs and opportunities related to target populations, endpoints, treatment durations, and target labels. By fostering precompetitive dialogue on clinical development for LRRK2-targeted therapies, MJFF sought to ensure that sponsors design robust and informative clinical trials that can accelerate drug development and meaningfully advance efforts to deliver effective treatments to patients. In this study, the authors highlight the topics discussed in the workshop and outline the roundtable participants' immediate- and medium-term goals for advancing LRRK2-targeted research and therapeutic development. Key immediate actions mentioned during the roundtable include developing a comprehensive inventory of existing LRRK2 cohorts and their associated clinical and biologic data and biospecimens to find opportunities for data acquisition and harmonization. The authors also discuss what participants cited as the need to develop and validate LRRK2 pathway biomarkers to facilitate population identification and assessment of therapeutic efficacy, and to use these biomarkers to identify "LRRK2-like" individuals with idiopathic Parkinson's disease who exhibit LRRK2 pathway dysfunction.