Recent advances in understanding amyotrophic lateral sclerosis and emerging therapies.
Recent advances in understanding amyotrophic lateral sclerosis and emerging therapies.
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DOI：
10.12703/b/9-12
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sattler R
中科院分区：
文献类型：
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作者：
Gittings LM;Sattler R
肌萎缩侧索硬化症（amyotrophic lateral sclerosis，ALS）是一种以上、下运动神经元变性和肌肉功能进行性丧失为特征的神经退行性疾病。在过去的十年中，在理解疾病的病因学和病理生物学方面取得了重大进展;然而，治疗选择仍然有限，只有两种对生存率有适度影响的药物在美国被批准用于ALS治疗。因此，对有效ALS疗法的研究仍在继续，针对ALS患者的60多项临床试验正在进行中，其他疗法处于临床前开发阶段。在了解ALS的遗传学、病理学和分子机制方面的最新进展已经导致了正在新兴ALS治疗干预中使用的新靶点和策略的鉴定。在这里，我们回顾了临床前或早期临床开发中新兴ALS疗法的现状和作用机制，包括基因治疗，免疫治疗和针对神经炎症，相分离和蛋白质清除的策略。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by degeneration of both upper and lower motor neurons and subsequent progressive loss of muscle function. Within the last decade, significant progress has been made in the understanding of the etiology and pathobiology of the disease; however, treatment options remain limited and only two drugs, which exert a modest effect on survival, are approved for ALS treatment in the US. Therefore, the search for effective ALS therapies continues, and over 60 clinical trials are in progress for patients with ALS and other therapeutics are at the pre-clinical stage of development. Recent advances in understanding the genetics, pathology, and molecular mechanisms of ALS have led to the identification of novel targets and strategies that are being used in emerging ALS therapeutic interventions. Here, we review the current status and mechanisms of action of a selection of emerging ALS therapies in pre-clinical or early clinical development, including gene therapy, immunotherapy, and strategies that target neuroinflammation, phase separation, and protein clearance.