Hydrogen sulfide as a therapeutic option for the treatment of Duchenne muscular dystrophy and other muscle-related diseases

Abstract

AbstractHydrogen sulfide (H2S) has been known for years as a poisoning gas and until recently evoked mostly negative associations. However, the discovery of its gasotransmitter functions suggested its contribution to various physiological and pathological processes. Although H2S has been found to exert cytoprotective effects through modulation of antioxidant, anti-inflammatory, anti-apoptotic, and pro-angiogenic responses in a variety of conditions, its role in the pathophysiology of skeletal muscles has not been broadly elucidated so far. The classical example of muscle-related disorders is Duchenne muscular dystrophy (DMD), the most common and severe type of muscular dystrophy. Mutations in the DMD gene that encodes dystrophin, a cytoskeletal protein that protects muscle fibers from contraction-induced damage, lead to prominent dysfunctions in the structure and functions of the skeletal muscle. However, the main cause of death is associated with cardiorespiratory failure, and DMD remains an incurable disease. Taking into account a wide range of physiological functions of H2S and recent literature data on its possible protective role in DMD, we focused on the description of the ‘old’ and ‘new’ functions of H2S, especially in muscle pathophysiology. Although the number of studies showing its essential regulatory action in dystrophic muscles is still limited, we propose that H2S-based therapy has the potential to attenuate the progression of DMD and other muscle-related disorders.