Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, 303 E Superior SQ 5-516, Chicago, IL, 60611, USA.
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Sci Rep. 2024 Nov 20;14(1):28745. doi: 10.1038/s41598-024-79024-8.
Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis. WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint. At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids decreased muscle proteins and increased certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy.
每周类固醇治疗肌肉疾病（WSiMD）是一项初步研究，旨在评估每周一次给予泼尼松龙治疗肢带型和贝克型肌营养不良症（LGMD 和 BMD）患者的疗效。研究终点时，患者的瘦体重增加、体脂减少、肌酸激酶降低，运动功能改善。该研究是受在肌肉营养不良症小鼠模型中进行的研究的启发，这些研究表明每周一次给予糖皮质激素可增强肌肉力量并减少纤维化。WSiMD 参与者在基线和每周类固醇治疗 6 个月时提供了用于适体血清分析的血液样本。一部分人在研究开始和结束时完成了肌肉磁共振（MR）评估。与年龄和性别匹配的健康对照组相比，WSiMD 队列的总血清蛋白谱以肌肉蛋白为主，反映出肌肉蛋白渗漏到血清中。与类固醇治疗效果相比，疾病状态导致更多的蛋白在血清中差异表达。尽管如此，即使在低剂量下，WSiMD 队列中也可观察到泼尼松龙的反应。糖皮质激素可降低肌肉蛋白并增加某些免疫过程和基质相关蛋白。肌肉 MR 脂肪分数与功能状态呈趋势相关。具有泼尼松龙反应性的标志物可用于更大规模的泼尼松龙疗效试验。
