The clinical trial landscape in amyotrophic lateral sclerosis-Past, present, and future.
The clinical trial landscape in amyotrophic lateral sclerosis-Past, present, and future.
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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。
DOI：
10.1002/med.21661
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发表时间：
2020
影响因子：
13.3
通讯作者：
Shorter,James
中科院分区：
文献类型：
--
作者：
Wobst,HeikeJ;Mack,KorrieL;Brown,DeanG;Brandon,NicholasJ;Shorter,James
肌萎缩侧索硬化症是一种以肌肉功能进行性丧失为特征的致死性神经退行性疾病。它是最常见的成人起病形式的运动神经元疾病，仅在美国就影响了大约16000 人。平均生存期为3年左右。到目前为止，只有两种介入性药物，即抗谷氨酸能的小分子利鲁唑和最近的抗氧化剂依达拉奉被批准用于治疗ALS。临床试验中正在调查的治疗策略涵盖一系列不同的方式和目标，到目前为止，已在临床上测试了70多种不同的药物。在这里，我们根据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，并强调了新出现的临床前策略，这些策略可能在抗击这种无情的疾病的战斗中提供突破。
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.