AUTHOR=Kelly Kaela , West Andrew B. 

TITLE=Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00807

DOI=10.3389/fnins.2020.00807

ISSN=1662-453X

ABSTRACT=<p>Genetic studies have identified variants in the <italic>LRRK2</italic> gene as important components of Parkinson’s disease (PD) pathobiology. Biochemical and emergent biomarker studies have coalesced around LRRK2 hyperactivation in disease. Therapeutics that diminish LRRK2 activity, either with small molecule kinase inhibitors or anti-sense oligonucleotides, have recently advanced to the clinic. Historically, there have been few successes in the development of therapies that might slow or halt the progression of neurodegenerative diseases. Over the past few decades of biomedical research, retrospective analyses suggest the broad integration of informative biomarkers early in development tends to distinguish successful pipelines from those that fail early. Herein, we discuss the biomarker regulatory process, emerging LRRK2 biomarker candidates, assays, underlying biomarker biology, and clinical integration.</p>