Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive loss of muscle function. It is the most common adult‐onset form of motor neuron disease, affecting about 16 000 people in the United States alone. The average survival is about 3 years. Only two interventional drugs, the antiglutamatergic small‐molecule riluzole and the more recent antioxidant edaravone, have been approved for the treatment of ALS to date. Therapeutic strategies under investigation in clinical trials cover a range of different modalities and targets, and more than 70 different drugs have been tested in the clinic to date. Here, we summarize and classify interventional therapeutic strategies based on their molecular targets and phenotypic effects. We also discuss possible reasons for the failure of clinical trials in ALS and highlight emerging preclinical strategies that could provide a breakthrough in the battle against this relentless disease.

中文翻译：

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肌萎缩侧索硬化症的临床试验前景——过去、现在和未来。


肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是肌肉功能进行性丧失。它是最常见的成人发病形式的运动神经元疾病，仅在美国就有约 16,000 人受到影响。平均生存期约为3年。迄今为止，只有两种介入药物被批准用于治疗 ALS，即抗谷氨酸能小分子利鲁唑和较新的抗氧化剂依达拉奉。临床试验中正在研究的治疗策略涵盖了一系列不同的模式和目标，迄今为止已有 70 多种不同的药物在临床上进行了测试。在这里，我们根据介入治疗策略的分子靶点和表型效应对介入治疗策略进行总结和分类。我们还讨论了 ALS 临床试验失败的可能原因，并强调了新兴的临床前策略，这些策略可以为对抗这种无情的疾病提供突破。