Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo, SP, Brazil.
Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):249-256. doi: 10.1590/0004-282X-ANP-2022-S135.
Monogenic neuromuscular disorders are potentially treatable through gene therapy. Using viral vectors, a therapeutic transgene aims to restore normal levels of a protein not produced by the defective gene, or to silence a gene whose expression leads to toxic effects. Spinal Muscular Atrophy (SMA) is a good example of a monogenic disease that currently has an AAV9-based vector gene therapy as a therapeutic option. In this review, we intend to discuss the viral vectors and their mechanisms of action, in addition to reviewing the clinical trials that supported the approval of gene therapy (AVXS-101) for SMA as well as neuromuscular diseases that are potentially treatable with gene replacement therapy.
单基因神经肌肉疾病可以通过基因治疗进行潜在治疗。使用病毒载体，治疗性转基因的目的是恢复未受缺陷基因影响的蛋白质的正常水平，或者沉默表达导致毒性作用的基因。脊髓性肌萎缩症（SMA）是单基因疾病的一个很好的例子，目前有基于 AAV9 的载体基因治疗作为一种治疗选择。在这篇综述中，我们打算讨论病毒载体及其作用机制，此外还回顾了支持 SMA 以及其他可能通过基因替代治疗进行治疗的神经肌肉疾病的基因治疗（AVXS-101）的临床试验。
