Current therapeutic approaches for Parkinson’s disease (PD) are based around treatments that alleviate symptoms but do not slow or prevent disease progression. As such, alternative strategies are needed. A promising approach is the use of molecules that reduce the function of LRRK2. Gain-of-function mutations in LRRK2 account for a notable proportion of familial PD cases, and significantly, elevated LRRK2 kinase activity is reported in idiopathic PD. Here, we describe progress in finding therapeutically effective LRRK2 inhibitors, summarising studies that range from in vitro experiments through to clinical trials. LRRK2 is a complex protein with two enzymatic activities and a myriad of functions. This creates opportunities for a rich variety of strategies, but also increases the risk of unintended consequences. We comment on the strength and limitations of the different approaches and conclude that with two molecules under clinical trial and a diversity of alternative options in the pipeline there is cause for optimism.This article is protected by copyright. All rights reserved.
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Daniel C Berwick