Implementation and Validation of Lysosome-specific Tests of GCase Activity in Cell Lines and Human Peripheral Blood

Study Rationale: Glucocerebrosidase (GCase) is an enzyme that is linked to Parkinson’s disease (PD) and is a high value target for disease-modifying treatments. Developing robust methods for accurately measuring GCase activity in relevant biosamples, such as peripheral blood, is paramount. The drawback of most current approaches is that they don’t measure GCase activity specifically in lysosomes, the subcellular compartment in which the enzyme normally functions.

Hypothesis: We hypothesize that a robust clinical assay for measuring GCase activity in the lysosome will be more accurate than conventional assays and will improve how we assess and follow up individuals with or at risk of PD.

Study Design: We will set up robust clinical tests for measuring lysosomal GCase activity in blood samples from people with PD and compare these tests with conventional approaches measuring GCase activity. In addition, we will use various drug compounds and cellular models to confirm the accuracy and effectiveness of our test.

Impact on Diagnosis/Treatment of Parkinson’s disease: We expect that our study will set a benchmark for measuring GCase activity in blood samples and that our methodologies will be easily adoptable for use by other researchers and clinicians.

Next Steps for Development: Next steps will include demonstrating its use across large-scale efforts in various clinical and research settings.