title: Histone deacetylase inhibitors in the treatment of muscular dystrophies: epigenetic drugs for genetic diseases.
abstract: Histone deacetylases inhibitors (HDACi) include a growing number of drugs that share the ability to inhibit the enzymatic activity of some or all the HDACs. Experimental and preclinical evidence indicates that these epigenetic drugs not only can be effective in the treatment of malignancies, inflammatory diseases and degenerative disorders, but also in the treatment of genetic diseases, such as muscular dystrophies. The ability of HDACi to counter the progression of muscular dystrophies points to HDACs as a crucial link between specific genetic mutations and downstream determinants of disease progression. It also suggests the contribution of epigenetic events to the pathogenesis of muscular dystrophies. Here we describe the experimental evidence supporting the key role of HDACs in the control of the transcriptional networks underlying the potential of dystrophic muscles either to activate compensatory regeneration or to undergo fibroadipogenic degeneration. Studies performed in mouse models of Duchenne muscular dystrophy (DMD) indicate that dystrophin deficiency leads to deregulated HDAC activity, which perturbs downstream networks and can be restored directly, by HDAC blockade, or indirectly, by reexpression of dystrophin. This evidence supports the current view that HDACi are emerging candidate drugs for pharmacological interventions in muscular dystrophies, and reveals unexpected common beneficial outcomes of pharmacological treatment or gene therapy.
authors.affiliation: Dulbecco Telethon Institute (DTI), IRCCS Fondazione Santa Lucia, and European Brain Research Institute, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Consalvi
authors.forename: Valentina
authors.initials: V
authors.lastname: Saccone
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Giordani
authors.forename: Giulia
authors.initials: G
authors.lastname: Minetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Mozzetta
authors.forename: Pier Lorenzo
authors.initials: PL
authors.lastname: Puri
mesh_terms: D000818:Animals; D016189:Dystrophin / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D009136:Muscular Dystrophies / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D016189:Dystrophin; D056572:Histone Deacetylase Inhibitors