Willis Alexander B, Zelikovich Aaron S, Sufit Robert, Ajroud-Driss Senda, Vandenborne Krista, Demonbreun Alexis R, Batra Abhinandan, Walter Glenn A, McNally Elizabeth M
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Dept of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL.
medRxiv. 2024 Jun 16:2024.06.14.24308858. doi: 10.1101/2024.06.14.24308858.
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.
RESULTS/CONCLUSIONS: 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 downregulated muscle proteins and upregulated 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.
肌肉萎缩症每周使用类固醇（WSiMD）是一项初步研究，旨在评估肢带型和贝克型肌肉萎缩症（分别为LGMD和BMD）患者每周一次使用泼尼松的情况。在研究终点时，出现了瘦体重增加、脂肪量减少、肌酸激酶降低和运动功能改善的趋势。该研究的动机来自于对小鼠肌肉萎缩症模型的研究，在这些模型中，每周一次暴露于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使用类固醇6个月后提供血样用于适配体血清分析。一部分参与者在研究开始和终点时完成了肌肉的磁共振（MR）评估。
结果/结论：与年龄和性别匹配的健康对照相比，在基线时，WSiMD队列中的总血清蛋白谱以肌肉蛋白为主，反映了肌肉蛋白泄漏到血清中。与类固醇治疗效果相比，疾病状态导致血清中差异存在的蛋白质更多。尽管如此，即使在低剂量下，WSiMD队列中对泼尼松的反应也是可辨别的。糖皮质激素下调肌肉蛋白并上调某些与免疫过程和基质相关的蛋白。肌肉MR脂肪分数与功能状态呈趋势相关。对泼尼松有反应的标志物可用于更大规模的泼尼松疗效试验。
