The LRRK2 detection initiative (LDI) and Rab detection initiative (RDI) are focused on developing techniques for the robust and sensitive detection of LRRK2, phospho-LRRK2, Rab and phospho-Rab in human biosamples to advance LRRK2 and Rabs as biomarkers of disease and of LRRK2 target engagement.
Measures of LRRK2 and phospho-LRRK2, as well as measures of the LRRK2 substrates of the Rab-GTPase family, are hypothesized to be linked to the development of Parkinson's disease (PD) and the inhibition of the LRRK2 kinase activity.
We will generate optimized LRRK2 recombinant protein standards and optimize sample processing procedures for urine and cerebrospinal fluid (clear liquid in the brain and spinal cord). We will also establish methods to detect Rab and phospho-Rab and apply these to human and pre-clinical models. If we are successful in detecting Rab in those sample types, we will test whether Rab or phospho-Rab are altered in individuals with PD and in pre-clinical models treated with LRRK2 kinase inhibitors.
Impact on Diagnosis/Treatment of Parkinson's disease:
LRRK2 and Rab proteins are strong candidate PD biomarkers and are biomarkers of pharmacodynamic response to LRRK2-targeting PD therapeutics.
Next Steps for Development:
If this project is successful, LRRK2 and Rab detection in biofluids will accelerate clinical trials and studies for PD therapeutics and ultimately be used as routine diagnostic tests for PD.