Institut National de la Santé et de la Recherche Médicale (INSERM/UEPS) UMR 861, Université d'Evry/ Paris Saclay, I-Stem, AFM 91100 Corbeil-Essonnes, France.
Cells. 2023 Feb 10;12(4):571. doi: 10.3390/cells12040571.
Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease caused by the expansion of a CTG repeat tract within the 3' untranslated region (3' UTR) of the dystrophia myotonica protein kinase gene (). Although DM1 is considered to be the most frequent myopathy of genetic origin in adults, DM1 patients exhibit a vast diversity of symptoms, affecting many different organs. Up until now, different in vitro models from patients' derived cells have largely contributed to the current understanding of DM1. Most of those studies have focused on muscle physiopathology. However, regarding the multisystemic aspect of DM1, there is still a crucial need for relevant cellular models to cover the whole complexity of the disease and open up options for new therapeutic approaches. This review discusses how human pluripotent stem cell-based models significantly contributed to DM1 mechanism decoding, and how they provided new therapeutic strategies that led to actual phase III clinical trials.
肌强直性营养不良 1 型（DM1）是一种进行性多系统疾病，由肌强直性营养不良蛋白激酶基因（）3'非翻译区（3'UTR）内 CTG 重复序列的扩展引起。尽管 DM1 被认为是成人中最常见的遗传性肌病，但 DM1 患者表现出广泛的不同症状，影响许多不同的器官。到目前为止，来自患者来源细胞的不同体外模型极大地促进了对 DM1 的当前理解。这些研究大多集中在肌肉病理生理学上。然而，关于 DM1 的多系统方面，仍然需要相关的细胞模型来涵盖疾病的全部复杂性，并为新的治疗方法开辟选择。这篇综述讨论了基于人类多能干细胞的模型如何极大地促进了 DM1 机制的解码，以及它们如何提供新的治疗策略，从而导致实际的 III 期临床试验。
