Burrow K L, Coovert D D, Klein C J, Bulman D E, Kissel J T, Rammohan K W, Burghes A H, Mendell J R
Department of Neurology, College of Medicine, Ohio State University, Columbus.
Neurology. 1991 May;41(5):661-6. doi: 10.1212/wnl.41.5.661.
The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript.
泼尼松改善杜氏肌营养不良症（DMD）患者肌肉力量和功能的机制尚不清楚。我们探讨了临床改善是否与泼尼松诱导的骨骼肌肌营养不良蛋白改变有关。在一项为期6个月的泼尼松随机双盲试验结束时，我们对患者进行了肌肉活检，并使用蛋白质免疫印迹法和组织切片抗体染色分析了肌营养不良蛋白的含量。这些研究表明，治疗组（泼尼松1.5mg/kg/d，n = 12；泼尼松0.75mg/kg/d，n = 9）和安慰剂组（n = 12）之间的肌营养不良蛋白含量没有显著差异。然而，有趣的是，在超过一半的杜氏患者的抗体染色组织切片中，存在数量不等的单个或成簇出现的肌营养不良蛋白阳性纤维（回复体）。突变分析显示，回复体出现在有可识别缺失或重复的DMD患者以及无缺失的患者中。泼尼松治疗并未影响回复体的发生率。回复体很可能是由于体细胞中发生的第二位点突变，使得肌营养不良蛋白转录本的翻译阅读框得以恢复。
