Department of Biosciences, University of Milan, Via Celoria 26, 20133, Milan, Italy.
Department of Biosciences, University of Milan, Via Celoria 26, 20133, Milan, Italy.
Exp Cell Res. 2022 Jan 15;410(2):112968. doi: 10.1016/j.yexcr.2021.112968. Epub 2021 Dec 7.
Muscular dystrophies (MDs) are heterogeneous diseases, characterized by primary wasting of skeletal muscle, which in severe cases, such as Duchenne Muscular Dystrophy (DMD), leads to wheelchair dependency, respiratory failure, and premature death. Research is ongoing to develop efficacious therapies, particularly for DMD. Most of the efforts, currently focusing on correcting or restoring the primary defect of MDs, are based on gene-addition, exon-skipping, stop codon read-through, and genome-editing. Although promising, most of them revealed several practical limitations. Shared knowledge in the field is that, in order to be really successful, any therapeutic approach has to rely on spared functional muscle tissue, restricting the number of patients eligible for clinical trials to the youngest and less compromised individuals. In line with this, many therapeutic strategies aim to preserve muscle tissue and function. This Review outlines the most interesting and recent studies addressing the secondary outcomes of DMD and how to better deliver the therapeutic agents. In the future, the effective treatment of DMD will likely require combinations of therapies addressing both the primary genetic defect and its consequences.
肌肉萎缩症（MDs）是一组异质性疾病，其特征为骨骼肌原发性萎缩，在严重的情况下，如杜氏肌营养不良症（DMD），会导致患者依赖轮椅、呼吸衰竭和过早死亡。目前正在进行研究以开发有效的治疗方法，特别是针对 DMD。大多数研究目前都集中在纠正或恢复 MD 的主要缺陷上，这些方法主要基于基因添加、外显子跳跃、终止密码子通读和基因组编辑。尽管这些方法很有前景，但大多数方法都暴露出了一些实际的局限性。该领域的共识是，为了真正取得成功，任何治疗方法都必须依赖于保留的功能性肌肉组织，这将限制有资格参加临床试验的患者数量仅限于最年轻和受影响最小的个体。因此，许多治疗策略旨在保护肌肉组织和功能。这篇综述概述了针对 DMD 的次要结果以及如何更好地递送治疗药物的最有趣和最新的研究。未来，DMD 的有效治疗可能需要结合治疗方法，既要针对主要的遗传缺陷，又要针对其后果。
