LAUSR

ABSTRACT Mutations in Leucine-rich repeat kinase 2 (LRRK2) are a risk factor for and a cause of sporadic and familial Parkinson’s disease (PD), respectively. These mutations are some of the most common genetic contributors to PD and render the kinase hyperactive. Increasingly within the past decade, there has been substantial effort investigating LRRK2 as a target for therapeutics in preclinical studies, and currently, small-molecule inhibitors and antisense oligonucleotides are being assessed in clinical trials as therapies to reduce the toxic hyperactivity of its kinase and/or reduce total levels of the protein in healthy individuals and people with PD. Areas covered In this review, we will provide an update on the current status of drugs and other technologies that have emerged in recent years and provide an overview of their efficacy in ameliorating LRRK2 kinase activity and overall safety in animal models and humans. Expert opinion The growth of both target discovery and innovative drug design has sparked a lot of excitement for the future of how we treat Parkinson’s disease. Given the immense focus on LRRK2 as a therapeutic target, it is expected within the next decade to determine its therapeutic properties, or lack thereof, for PD.