Objective/Rationale:
Inherited mutations in the enzyme LRRK2 are known to cause Parkinson’s disease (PD). Measuring the enzyme activity of LRRK2 in patient biological samples is difficult due to the lack of sensitivity of current assay techniques; this represents an unmet need. We will develop sensitive assays of LRRK2 activity in patient samples in order to allow for the assessment of LRRK2 activity in PD patients as a potential biomarker for disease and for evaluation of LRRK2 targeting drugs in a potential clinical trial.
Project Description:
In collaboration with LifeTechnologies, we will apply novel techniques that enhance antibody based detection of signaling events within cells. We will develop multiple probes for LRRK2 kinase activity and several intermolecular interactions. These assays will be evaluated in a variety of LRRK2 expression platforms to ensure efficacy in detecting differences in LRRK2 kinase activity. We will also ascertain patient derived biological samples from a small cohort of control and idiopathic PD patients for a proof of principle evaluation of assay effectiveness.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Small molecule inhibitors of LRRK2 kinase activity are hypothesized to be a potential therapeutic for PD. Changes in the level of LRRK2 kinase activity may serve as a predictor of PD. Our sensitive assays of LRRK2 activity in patient samples will allow for the assessment of LRRK2 activity as a potential biomarker for disease and for evaluation of LRRK2 targeting drugs in a potential clinical trial.
Anticipated Outcome:
We will establish a sensitive assay for detecting LRRK2 activity in patient samples. These assays will allow for the exploration of LRRK2 kinase activity as a biomarker of PD. These assays could also serve as a surrogate marker for compound efficacy during a clinical trial surrounding a LRRK2 targeting compound.