Genetic-Based Treatment Strategies for Muscular Dystrophy and Congenital Myopathies.
Genetic-Based Treatment Strategies for Muscular Dystrophy and Congenital Myopathies.
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DOI：
10.1212/con.0000000000001203
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发表时间：
2022-12-01
期刊：
影响因子：
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通讯作者：
Weihl, Conrad C
中科院分区：
文献类型：
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作者：
Findlay, Andrew R;Weihl, Conrad C
本文讨论了神经肌肉医学中基因治疗策略的基本概念，以及基因检测作为应用基因治疗的必要条件的重要性。基因疗法已经成为一些神经肌肉疾病的现实。外显子跳脱和（在欧洲）核糖体读通方法目前可用于杜氏肌营养不良症的一部分患者。微营养不良蛋白基因替代已显示出希望，并已接近临床试验的最后阶段。许多其他肌肉萎缩症和先天性肌病的基因疗法也正在获得批准。肌营养不良症和先天性肌病是一种异质性的遗传性肌肉疾病。通过基因检测确认诊断不仅对指导治疗至关重要，而且是当前和未来基因治疗的实际前提。隐性功能丧失或显性单倍功能不全疾病可以用基因替代策略治疗，而显性阴性和毒性功能获得疾病最好通过各种敲低方法来解决。重要的是要认识到许多治疗方法是突变特异性的，只对患有特定疾病的一小部分个体有益。
This article discusses the foundational concepts of genetic treatment strategies employed in neuromuscular medicine, as well as the importance of genetic testing as a requirement for applying gene-based therapy. Gene therapies have become a reality for several neuromuscular disorders. Exon-skipping and (in Europe) ribosomal read-through approaches are currently available to a subset of patients with Duchenne muscular dystrophy. Microdystrophin gene replacement has shown promise and is nearing the final stages of clinical trials. Numerous gene-based therapies for other muscular dystrophies and congenital myopathies are progressing toward approval as well. Muscular dystrophies and congenital myopathies are a heterogenous group of hereditary muscle disorders. Confirming a diagnosis with genetic testing is not only critical for guiding management, but also an actual prerequisite for current and future gene therapies. Recessive loss-of-function or dominant haploinsufficiency disorders may be treated with gene replacement strategies, whereas dominant negative and toxic gain-of-function disorders are best addressed with a variety of knockdown approaches. It is important to recognize that many therapeutics are mutation specific and will only benefit a subset of individuals with a specific disease.