Institute for Health and Sport (IHeS), Victoria University, Melbourne, Victoria, Australia.
Australian Institute for Musculoskeletal Science (AIMSS), St Albans, Victoria, Australia.
JCI Insight. 2023 Nov 8;8(21):e165974. doi: 10.1172/jci.insight.165974.
New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable. Here, we tested 2 weeks of daily 100 mg/kg DMF versus 5 mg/kg standard-care prednisone (PRED) treatment in juvenile mdx mice with early symptomatic DMD. Both drugs modulated seed genes driving the DMD disease program and improved force production in fast-twitch muscle. However, only DMF showed pro-mitochondrial effects, protected contracting muscles from fatigue, improved histopathology, and augmented clinically compatible muscle function tests. DMF may be a more selective modulator of the DMD disease program than PRED, warranting follow-up longitudinal studies to evaluate disease-modifying impact.
需要新的药物来治疗致命的神经肌肉疾病杜氏肌营养不良症（DMD）。富马酸二甲酯（DMF）是一种有效的免疫调节小分子核红细胞 2 相关因子 2 激活剂，目前在多发性硬化症和银屑病的治疗中有临床应用，对 DMD 可能有效，并且可以快速转化。在这里，我们测试了每日 100mg/kg DMF 与 5mg/kg 标准治疗泼尼松龙（PRED）在早期有症状的 mdx 幼鼠中的治疗效果，持续 2 周。两种药物均调节了驱动 DMD 疾病进程的种子基因，并改善了快肌的肌力。然而，只有 DMF 表现出促线粒体作用，可保护收缩肌肉免受疲劳，改善组织病理学，并增强临床相容的肌肉功能测试。DMF 可能是 DMD 疾病进程的更具选择性调节剂，需要进行后续的纵向研究来评估其对疾病的改善作用。
