Elevated In Vitro Kinase Activity in Peripheral Blood Mononuclear Cells of Leucine‐Rich Repeat Kinase 2 G2019S Carriers: A Novel Enzyme‐Linked Immunosorbent Assay–Based Method

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Abstract

Background

Leucine‐rich repeat kinase 2 kinase inhibitors are being vigorously pursued as potential therapeutic options; however, there is a critical need for sensitive and quantitative assays of leucine‐rich repeat kinase 2 function and target engagement.

Objectives

Our objective was to compare collection and storage protocols for peripheral blood mononuclear cells, and to determine the optimal conditions for downstream analyses of leucine‐rich repeat kinase 2 in PD cohorts.

Methods

Here, we describe enzyme‐linked immunosorbent assay–based assays capable of detecting multiple aspects of leucine‐rich repeat kinase 2 function at endogenous levels in human tissues.

Results

In peripheral blood mononuclear cells from both healthy and affected carriers of the G2019S mutation in leucine‐rich repeat kinase 2, we report, for the first time, significantly elevated in vitro kinase activity, while detecting a significant increase in pS935/leucine‐rich repeat kinase 2 in idiopathic PD patients.

Conclusions

Quantitative assays such as these described here could potentially uncover specific markers of leucine‐rich repeat kinase 2 function that are predictive of disease progression, aid in patient stratification, and be a critical component of upcoming clinical trials. © 2020 International Parkinson and Movement Disorder Society

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