Guidance on LRRK2 Biofluid Biomarkers for use in LRRK2 Clinical Trials

This document summarizes guidance developed through the Michael J. Fox Foundation's (MJFF) LRRK2 Therapeutics Investigative Exchange (LITE) initiative to support companies running LRRK2-targeted clinical trials, with the shared goal of accelerating therapeutic development. It outlines MJFF’s recommended use of target engagement, pathway engagement, disease, and exploratory biomarkers—particularly encouraging broad inclusion of available and emerging biomarkers in Phase 2 trials—and provides a detailed landscape of assays, biological matrices, and data availability, many of which are already generating or will soon generate data through PPMI and the LITE global consortium cohorts. The document also highlights exploratory biomarker platforms under evaluation within the LITE initiative (e.g., skin, breath, sebum, PBMCs) and emphasizes collaboration through assay sharing, validation in MJFF/LITE cohorts, and open data sharing across the consortium. Finally, it describes preferred collaboration models in Phase 2 trials to compare placebo and active arms for insights into target/pathway engagement and disease biology, while also noting how Phase 1 data in healthy controls and Parkinson’s disease participants can inform pharmacodynamic endpoints and de-risk subsequent trials.