Parkinson’s Research Project Title: Longitudinal validation of peripheral lysosomal GCase under clinical trial conditions

Principal Investigators: Nicolas Dzamko, PhD, Senior Research Fellow, Brain and Mind Centre

Institutions: University of Sydney

Co-Principal Investigators/Co-Principal Investigator institutions:

Antony Cooper (Garvan Institute); Simon J.G. Lewis (University of Sydney), Glenda Halliday (University of Sydney), Justin O’Sullivan (University of Auckland)

Study Rationale:

This Parkinson’s research project aims to further validate peripheral monocyte in situ lysosomal GCase activity as a PD biomarker. The research team have established a flow cytometry assay for the specific measurement of lysosomal GCase activity in blood cells and shown that monocyte lysosomal GCase activity is reduced in PD patients, or at least a subset of PD patients. This could make peripheral lysosomal GCase activity useful for stratification of patients into trials targeting GCase, for monitoring pharmacodynamic responses to clinical trial drugs and/or monitoring progression of PD. However, longitudinal assessment of GCase activity using this method has not been performed and little is known about how preanalytical factors may affect measurements. As part of on Australian Parkinson’s Mission clinical trial peripheral blood mononuclear cells (PBMCs) have been cryopreserved from participants at baseline, mid trial (24 weeks), end of treatment (48 weeks), and after a washout period (60 weeks). The researchers propose to use these samples to longitudinally assess monocyte GCase activity over the duration of a typical clinical trial using the GCase probe PFB-FDglu.