Clinical Use of Immunosuppressants in Duchenne Muscular Dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a degenerative disease primarily affecting voluntary muscles with secondary consequences on heart and breathing muscles. DMD is an X-linked recessive disease that results in the loss of dystrophin, a key muscle protein. Inflammation can play different roles in DMD; it can be a secondary response to muscle degeneration, a primary cause of degeneration, or can contribute to the disease progression. Several immunosuppressants have been used with the aim to reduce the inflammation associated with DMD. Most recently, myoblast transplantation has shown the possibility to restore the dystrophin lack in the DMD patient's muscle fibers and this evidence has emphasized the importance of the use of immunosuppressants and the necessity of studying them and their secondary effects. The aim of this review is to analyze the main immunosuppressants drugs starting from the mdx mice experiments and concluding with the most recent human clinical studies.

Rapamycin Ameliorates Dystrophic Phenotype in mdx Mouse Skeletal Muscle

“…The effects of different immunosuppressant drugs, including cyclosporine A, prednisone and deflazacort, have been investigated in dystrophin-deficient muscles, as reviewed by Iannitti et al (27) The study presented here, however, is the first report of RAPA treatment for dystrophin-deficient skeletal muscle of the mdx murine model for DMD, a model in which a genetic defect in dystrophin expression promotes inflammatory cell infiltration in muscle tissue.…”

Tissue Tregs

“…Their function has not been well studied, although both CD4 + and CD8 + T cells seem to promote the mdx pathology, and blocking their activities with immunosuppressants can ameliorate disease (72). For example, local or systemic treatment with rapamycin improves the mdx phenotype, with concomitant decreases in infiltrating CD4 + and CD8 + effector T cell populations, while Tregs remain stable (73).…”

Flavocoxid, a Nutraceutical Approach to Blunt Inflammatory Conditions

“…The disease results from absence of the protein dystrophin, which is an essential component of the dystrophin-glycoprotein complex that maintains membrane integrity of muscle fibers by linking cytoskeleton to extracellular matrix. Muscle degeneration in muscle dystrophy is exacerbated by the endogenous inflammatory response and increased oxidative stress, and NF- κ B plays a pivotal role in orchestrating this inflammatory cascade [38, 39]. The effects of flavocoxid were studied in a comparison study with methylprednisolone, the gold standard treatment for DMD patients, using the mdx mice, the murine model of DMD [37].…”