Wilton-Clark Harry, Yokota Toshifumi
Faculty of Medicine and Dentistry, Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
Expert Opin Biol Ther. 2023 Jan;23(1):49-59. doi: 10.1080/14712598.2022.2150543. Epub 2022 Dec 1.
Duchenne muscular dystrophy is a lethal genetic disease which currently has no cure, and poor standard treatment options largely focused on symptom relief. The development of multiple biological and genetic therapies is underway across various stages of clinical progress which could markedly affect how DMD patients are treated in the future.
The purpose of this review is to provide an introduction to the different therapeutic modalities currently being studied, as well as a brief description of their progress to date and relative advantages and disadvantages for the treatment of DMD. This review discusses exon skipping therapy, microdystrophin therapy, stop codon readthrough therapy, CRISPR-based gene editing, cell-based therapy, and utrophin upregulation. Secondary therapies addressing nonspecific symptoms of DMD were excluded.
Despite the vast potential held by gene replacement therapy options such as microdystrophin production and utrophin upregulation, safety risks inherent to the adeno-associated virus delivery vector might hamper the clinical viability of these approaches until further improvements can be made. Of the mutation-specific therapies, exon skipping therapy remains the most extensively validated and explored option, and the cell-based CAP-1002 therapy may prove to be a suitable adjunct therapy filling the urgent need for cardiac-specific therapies.
杜氏肌营养不良症是一种致命的遗传疾病，目前尚无治愈方法，现有的标准治疗方案效果不佳，主要侧重于缓解症状。多种生物和基因疗法正处于不同的临床进展阶段，这可能会显著影响未来杜氏肌营养不良症患者的治疗方式。
本综述旨在介绍目前正在研究的不同治疗方式，简要描述其迄今取得的进展以及治疗杜氏肌营养不良症的相对优缺点。本综述讨论了外显子跳跃疗法、微肌营养不良蛋白疗法、终止密码子通读疗法、基于CRISPR的基因编辑、细胞疗法和上调抗肌萎缩蛋白。排除了针对杜氏肌营养不良症非特异性症状的辅助疗法。
尽管诸如生产微肌营养不良蛋白和上调抗肌萎缩蛋白等基因替代疗法具有巨大潜力，但腺相关病毒递送载体固有的安全风险可能会阻碍这些方法的临床可行性，直到能够进一步改进。在针对特定突变的疗法中，外显子跳跃疗法仍然是最广泛验证和探索的选择，基于细胞的CAP-1002疗法可能被证明是一种合适的辅助疗法，满足对心脏特异性疗法的迫切需求。
