Genetic studies have identified variants in the LRRK2 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.

中文翻译：

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用于新兴 LRRK2 疗法的药效生物标志物

遗传研究已确定 LRRK2 基因中的变异是帕金森病 (PD) 病理生物学的重要组成部分。生化和紧急生物标志物研究已围绕疾病中的 LRRK2 过度激活进行。使用小分子激酶抑制剂或反义寡核苷酸降低 LRRK2 活性的疗法最近已进入临床。从历史上看，在开发可能减缓或阻止神经退行性疾病进展的疗法方面几乎没有成功。在过去几十年的生物医学研究中，回顾性分析表明，在开发早期广泛整合信息性生物标志物倾向于区分成功的管道和早期失败的管道。在此，我们讨论了生物标志物监管过程、新兴的 LRRK2 生物标志物候选物、检测、