Study Rationale:
The goal of this project is to use standardized and validated samples to determine if the LRRK2 and pS1292 LRRK2 assays available through ADx Neurosciences can detect LRRK2 activity increases in G2019S-LRRK2 mutation carriers or decreases in individuals treated with LRRK2 kinase inhibitors.
Hypothesis:
The biochemical effects of the G2019S-LRRK2 mutation or LRRK2 kinase inhibitor treatment can be reliably measured in biofluids using the ADx Neurosciences assays.
Study Design:
Various samples will be prepared and validated for varying levels of total LRRK2 and pS1292 LRRK2. These include pre-clinical model brain samples, pre-clinical model CSF in a LRRK2 kinase inhibitor study, and CSF/serum samples from people with or without the LRRK2 G2019S mutation who are healthy or have Parkinson’s disease. Samples will analyzed on the ADx Neurosciences assays to determine if the assays are sensitive and specific enough to detect differences between samples.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Project success would facilitate both target engagement measures for LRRK2-linked therapies as well as future subject stratification for consideration in LRRK2-linked therapeutic trials.
Next Steps for Development:
If the assays detect LRRK2 activity changes, they could be employed in LRRK2 therapeutic initiatives to identify patients for inclusion in clinical trials or measure effects of LRRK2 therapies.