Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene resulting in the loss of the protein dystrophin. Although animal models, such as the MDX mouse and the golden retriever muscular dystrophy dog, have helped further understand DMD pathogenesis and guided treatment development, they do not fully recapitulate human disease. In Cell, Ren and colleagues describe a new gene-edited rhesus monkey model of DMD that displays progressive muscle deterioration and impaired motor function, as seen in human patients. Single-cell RNA sequencing analysis revealed several cellular changes in DMD skeletal muscles, including a dramatic increase in immune cells and profound alterations in fibro-adipogenic progenitors and muscle stem cells (MuSCs). MuSCs from DMD animals notably showed differentiation deficiencies and increased fibrosis levels compared to wild-type cells. In addition to providing a more advanced animal model of DMD, this new study offers new clues on the pathogenesis of the disease, which could lead to new treatment strategies.

Original reference: Ren, S. et al. Cell https://doi.org/10.1016/j.cell.2024.08.041 (2024)

杜氏肌营养不良症 （DMD） 是一种由 DMD 基因突变引起的 X 连锁疾病，导致抗肌萎缩蛋白蛋白丢失。尽管动物模型（如 MDX 小鼠和金毛猎犬肌肉萎缩症犬）有助于进一步了解 DMD 发病机制并指导治疗开发，但它们并不能完全概括人类疾病。在Cell中，任及其同事描述了一种新的基因编辑的恒河猴DMD模型，该模型显示出进行性肌肉退化和运动功能受损，如在人类患者中所见。单细胞 RNA 测序分析揭示了 DMD 骨骼肌的多种细胞变化，包括免疫细胞的急剧增加以及纤维成脂祖细胞和肌肉干细胞 （MuSCs） 的深刻改变。与野生型细胞相比，来自 DMD 动物的 MuSCs 明显显示出分化缺陷和纤维化水平增加。除了提供更先进的 DMD 动物模型外，这项新研究还为该疾病的发病机制提供了新线索，这可能导致新的治疗策略。

Original reference: Ren, S. et al. Cell https://doi.org/10.1016/j.cell.2024.08.041 (2024)