Mononuclear cell analysis of muscle biopsies in prednisone-treated and untreated Duchenne muscular dystrophy. CIDD Study Group.

A recent double-blind, placebo-controlled trial has shown that prednisone improves strength in patients with Duchenne muscular dystrophy. To determine whether immunosuppressant effects were important in mediating this improvement, we performed immunohistochemical analyses on muscle biopsies obtained at the conclusion of the trial. We studied 33 patients: 12 from the placebo group, nine from the low-dose prednisone group (0.75 mg/kg/d), and 12 from the high-dose group (1.5 mg/kg/d). There was a significant difference in total T cells (CD2+) between the placebo group and both treatment groups. Similarly, the number of CD8+ cytotoxic/suppressor T cells was significantly decreased in both treated groups compared with placebo. The number of muscle fibers focally invaded by lymphocytes was also significantly decreased in the two treated groups compared with controls. There were no differences between the low- and high-dose groups. The numbers of B cells, natural killer cells, CD4+ cells, macrophages, and necrotic muscle fibers were not significantly different in the treated and control groups. This study suggests that prednisone may improve strength in Duchenne muscular dystrophy through primarily immunologic mechanisms involving T lymphocytes.

Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group.

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.