Objective/Rationale:
It has been suggested that the G2019S mutation in the LRRK2 gene leads to increased kinase (a type of enzyme) activity. Previous work has been conducted in cultured cells, not in humans. The purpose of these proposed studies is to determine kinase activity in cell samples from human blood.
Project Description:
The goal of this project is to develop a test of LRRK2 kinase activity in lymphocytes (a kind of white blood cell) from frozen human blood samples. Samples from patients with PD carrying the LRRK2 G2019S mutation, patients with idiopathic (unknown cause) PD, and healthy controls will be obtained from the Harvard NeuroDiscovery Biomarker Study. LRRK2 will be derived from the samples and its kinase activity will be measured. Kinase activity in patients with PD carrying the LRRK2 G2019S mutation will be compared to activity in patients with idiopathic PD and healthy controls.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The lack of biological markers is a critical obstacle in the development of new therapeutics for Parkinson's disease. Monitoring LRRK2 kinase activity in lymphocytes could be a potential non-invasive biomarker for diagnosis, monitoring for disease progression, and treatment response of PD.
Anticipated Outcome:
The proposed work will determine whether lymphocytes can be used as a resource for monitoring normal and PD-relevant abnormal LRRK2 kinase activity.