Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Department of Comparative Biomedical Sciences, Neuromuscular Diseases Group, Royal Veterinary College, London, United Kingdom.
J Neuromuscul Dis. 2021;8(5):845-863. doi: 10.3233/JND-200524.
Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as it decreases development time. Recent studies suggested that simvastatin, a cholesterol lowering drug used for cardiovascular diseases, has beneficial effects on several parameters in mdx mice. To validate properly the effectiveness of simvastatin, two independent labs tested the effects of 12-week simvastatin treatment in either young (starting at 4 weeks of age) or adult (starting at 12 weeks of age) mdx mice. In neither study were benefits of simvastatin treatment observed on muscle function, histology or expression of genes involved in fibrosis, regeneration, oxidative stress and autophagy. Unexpectedly, although the treatment protocol was similar, simvastatin plasma levels were found to be much lower than observed in a previous study. In conclusion, in two laboratories, simvastatin did not ameliorate disease pathology in mdx mice, which could either be due to the ineffectiveness of simvastatin itself or due to the low simvastatin plasma levels following oral administration via the food.
杜氏肌营养不良症是一种 X 连锁隐性肌营养不良症，其特征是缺乏肌营养不良蛋白导致纤维化、炎症和氧化应激，从而导致肌肉组织丧失。药物再利用，即使用已经批准用于其他疾病的药物，具有吸引力，因为它可以缩短开发时间。最近的研究表明，辛伐他汀是一种用于心血管疾病的降胆固醇药物，对 mdx 小鼠的几个参数有有益的影响。为了正确验证辛伐他汀的有效性，两个独立的实验室测试了辛伐他汀治疗在年轻（从 4 周龄开始）或成年（从 12 周龄开始）mdx 小鼠中的 12 周的效果。在这两项研究中，都没有观察到辛伐他汀治疗对肌肉功能、组织学或纤维化、再生、氧化应激和自噬相关基因表达的有益影响。出乎意料的是，尽管治疗方案相似，但辛伐他汀的血浆水平却比以前的研究中观察到的要低得多。总之，在两个实验室中，辛伐他汀都没有改善 mdx 小鼠的疾病病理，这可能是由于辛伐他汀本身无效，也可能是由于口服食物后辛伐他汀的血浆水平较低所致。
