Anti-Inflammatory and General Glucocorticoid Physiology in Skeletal Muscles Affected by Duchenne Muscular Dystrophy: Exploration of Steroid-Sparing Agents

• Published in: International journal of molecular sciences Vol. 21; no. 13; p. 4596
• Main Authors: Herbelet, Sandrine, Rodenbach, Arthur, Paepe, Boel De, De Bleecker, Jan L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-06-2020; MDPI
• Subjects: Animal models; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Biomedical materials; Cell adhesion & migration; Chemokines; Clinical trials; Cytokines; Cytoplasm; Duchenne muscular dystrophy; Duchenne's muscular dystrophy; Free radicals; Gene expression; glucocorticoid physiology; Glucocorticoids; Glucocorticoids - pharmacology; Growth factors; Humans; Hyperglycemia; Hypertension; Immune system; Inflammation; Kinases; Metabolic rate; Metabolism; MicroRNAs; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Muscular dystrophy; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - pathology; Musculoskeletal system; Osteoporosis; Proteins; Review; Signal transduction; Skeletal muscle; steroid-sparing agents; Steroids; Steroids - metabolism; Transcription factors; Tumor necrosis factor-TNF; glucocorticoid physiology; steroid-sparing agents; skeletal muscle; Duchenne muscular dystrophy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21134596

In Duchenne muscular dystrophy (DMD), the activation of proinflammatory and metabolic cellular pathways in skeletal muscle cells is an inherent characteristic. Synthetic glucocorticoid intake counteracts the majority of these mechanisms. However, glucocorticoids induce burdensome secondary effects, including hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth delay, skin thinning, cushingoid appearance, and tissue-specific glucocorticoid resistance. Hence, lowering the glucocorticoid dosage could be beneficial for DMD patients. A more profound insight into the major cellular pathways that are stabilized after synthetic glucocorticoid administration in DMD is needed when searching for the molecules able to achieve similar pathway stabilization. This review provides a concise overview of the major anti-inflammatory pathways, as well as the metabolic effects of glucocorticoids in the skeletal muscle affected in DMD. The known drugs able to stabilize these pathways, and which could potentially be combined with glucocorticoid therapy as steroid-sparing agents, are described. This could create new opportunities for testing in DMD animal models and/or clinical trials, possibly leading to smaller glucocorticoids dosage regimens for DMD patients.