The goal of this study is to determine the effect of LRRK2 and GBA mutations on activities of both enzymes under basal/stimulated (pathogens) conditions and with and without LKIs and GCase activators using cryopreserved PBMCs  from patient cohorts (provided by Columbia University and Barcelona).  The co-Principal Investigators of this project, Malu Tansey and Nicholas Dzamko were previously funded to compare various PBMC and monocyte isolation protocols for detection of LRRK2 and GCase activities by flow and immunoblotting.

This supplement now utilizes the finalized protocol (cryopreserved PBMCs) to assess enzyme activities under basal/pathogen-stimulated conditions with and without LKIs and GCase activators in various PD cohorts. This study is an extension of three studies conducted in animal models indicating that LRRK2 and GCase activities can be easily detected and modulated in immune cells in response to immune triggers. The outcomes of these studies will indicate if GBA subjects would benefit from LRRK2 kinase inhibitors and vice versa and point to converging immune phenotypes (cytokines) in PBMCs from LRRK2 and GBA mutation carriers.

Two clinical sites (Columbia University- Roy Alcalay and Barcelona-Eduardo Tolosa) will provide PBMCs for this study.