Study Rationale: LRRK2 is a protein for which inappropriate activation is associated with Parkinson’s disease (PD). Investigators are therefore pursuing the activity of LRRK2 as a potential therapeutic target, for both familial and the more common idiopathic forms of PD. Several approaches to targeting LRRK2 are now entering clinical trials, and biomarker tools that can track LRRK2 inhibition are needed to support these studies. We are proposing a novel biomarker assay that can simultaneously measure up to four independent indicators of LRRK2 inhibition, providing a more comprehensive picture of the status of LRRK2 activity than is currently available.
Hypothesis: We hypothesize that our novel “multiplexed” biomarker assay, which is designed to provide up to four independent pharmacodynamic markers of LRRK2 inhibition, could act as a powerful tool to support ongoing clinical trials of new compounds targeting the kinase activity of LRRK2.
Study Design: In the first phase of the study, we will develop and validate our novel biomarker assay. In the second phase, we will assess the performance of the new assay in measuring the activation of this pathway in multiple types of samples (including blood cells and cerebrospinal fluid) from different cohorts of people with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this assay can help establish inclusion criteria for participation in clinical trials for LRRK2 inhibitors, provide four unique measures of target engagement to assess drug efficacy, offer rapid feedback to allow adjustment of dosing and, correlated with clinical motor and non-motor data, aid in disease tracking.
Next Steps for Development: Following validation of our assay’s performance in multiple sample types, we expect that the assay will be ready to be deployed in trials of new LRRK2 inhibitors. We can also work to further tailor or customize the assay with specific new or known targets.