Kelly Kaela, West Andrew B
Duke Center for Neurodegeneration Research, Departments of Pharmacology and Cancer Biology, Neurology, and Neurobiology, Duke University, Durham, NC, United States.
Front Neurosci. 2020 Aug 6;14:807. doi: 10.3389/fnins.2020.00807. eCollection 2020.
Genetic studies have identified variants in the 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.
基因研究已确定该基因中的变异是帕金森病（PD）病理生物学的重要组成部分。生物化学和新兴生物标志物研究聚焦于疾病中LRRK2的过度激活。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阶段。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鲜有成功案例。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丰富的生物标志物往往能区分成功的研发流程与早期失败的流程。在此，我们讨论生物标志物监管过程、新兴的LRRK2生物标志物候选物、检测方法、潜在的生物标志物生物学以及临床整合。
