RoleofHDAC4inmusculardystrophyandregeneration

The objectives of this proposal are to define the role of the protein Histone Deacetylase 4 (HDAC4) in muscular dystrophy and muscle repair, with the aim to provide new insights for developing more efficacious therapeutic approaches for the treatment of muscular dystrophies. Muscular dystrophy is a genetic, lethal, disorder characterized by the progressive loss of skeletal muscle tissue due to chronic damage combined with the decrease of the ability of the muscle to repair. Promoting muscle regeneration ameliorates muscular dystrophy. Unfortunately, to date, there is no effective cure. Among therapies, general HDAC inhibitors are on clinical trial, despite their broad range of action and their toxic effects for long-term treatment. By delineating the role of HDAC4, which is a repressor of gene transcription, in muscular dystrophy, we aim to design more specific drugs to fight muscular dystrophy. From our preliminary data, there are no doubts that HDAC4 plays a role in muscular dystrophy and muscle repair. Muscle repair is promoted by muscle stem cells that, upon stimuli, start proliferating and differentiating in adult muscle. HDAC4 regulates muscle stem cell proliferation and differentiation. In this proposal, we intend to identify which are the target genes controlled by HDAC4 in muscle stem cells, with the aim to improve muscle regneration in dystrophic conditions.