Katyal Nakul, Govindarajan Raghav
Neurology, University of Missouri School of Medicine, University of Missouri, Columbia, MO, United States.
Front Neurol. 2017 Sep 29;8:521. doi: 10.3389/fneur.2017.00521. eCollection 2017.
Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials. In this review, we have outlined the possible reasons for failure of ALS clinical trials, addressed the factors limiting timely diagnosis, and suggested possible solutions for future considerations for each of the shortcomings.
肌萎缩侧索硬化症（ALS）是一种临床上进行性发展的神经退行性综合征，主要影响运动神经元及其相关神经束。利鲁唑和依达拉奉是仅有的两种获得美国食品药品监督管理局（FDA）认证的治疗ALS的药物。在过去二十年中，几乎所有旨在为这种疾病制定成功治疗策略的临床试验都失败了。基因复杂性、动物模型不完善、临床试验设计不佳、缺乏敏感的生物标志物以及诊断延迟是限制ALS临床试验取得重大进展的一些潜在原因。在本综述中，我们概述了ALS临床试验失败的可能原因，探讨了限制及时诊断的因素，并针对每个缺点提出了未来可供考虑的可能解决方案。
