Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA.
Department of Neurology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Hum Gene Ther. 2023 May;34(9-10):345-349. doi: 10.1089/hum.2023.29242.ddu.
Duchenne muscular dystrophy (DMD) was named more than 150 years ago. About four decades ago, the gene was discovered, and the reading frame shift was determined as the genetic underpinning. These pivotal findings significantly changed the landscape of DMD therapy development. Restoration of dystrophin expression with gene therapy became a primary focus. Investment in gene therapy has led to the approval of exon skipping by regulatory agencies, multiple clinical trials of systemic microdystrophin therapy using adeno-associated virus vectors, and revolutionary genome editing therapy using the CRISPR technology. However, many important issues surfaced during the clinical translation of DMD gene therapy (such as low efficiency of exon skipping, immune toxicity-induced serious adverse events, and patient death). In this issue of , several research articles highlighted some of the latest developments in DMD gene therapy. Importantly, a collection of articles from experts in the field reviewed the progress, major challenges, and future directions of DMD gene therapy. These insightful discussions have significant implications for gene therapy of other neuromuscular diseases.
杜氏肌营养不良症（DMD）是 150 多年前命名的。大约 40 年前，该基因被发现，并且确定阅读框移码是其遗传基础。这些关键发现极大地改变了 DMD 治疗开发的格局。用基因治疗恢复肌营养不良蛋白的表达成为主要关注点。对基因治疗的投资导致了监管机构批准外显子跳跃，使用腺相关病毒载体进行全身性微肌营养不良蛋白治疗的多项临床试验，以及使用 CRISPR 技术的革命性基因组编辑治疗。然而，在 DMD 基因治疗的临床转化过程中出现了许多重要问题（例如外显子跳跃效率低、免疫毒性引起的严重不良事件和患者死亡）。本期《柳叶刀神经病学》杂志中的几篇研究文章重点介绍了 DMD 基因治疗的一些最新进展。重要的是，该领域专家的一系列文章回顾了 DMD 基因治疗的进展、主要挑战和未来方向。这些有见地的讨论对其他神经肌肉疾病的基因治疗具有重要意义。
