Molecular Medicine

, Volume 17, Issue 5–6, pp 457–465 | Cite as

Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases

  • Silvia Consalvi
  • Valentina Saccone
  • Lorenzo Giordani
  • Giulia Minetti
  • Chiara Mozzetta
  • Pier Lorenzo Puri
Review Article


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.



PL Puri is an Associate Telethon Scientist of the Dulbecco Telethon Institute (DTI) and Associate Investigator of San-ford Children’s Health Research Center. C Mozzetta is a recipient of AFM post-doc fellowship. The authors thank all members of PL Puri’s lab for productive discussion and comments during manuscript preparation.


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Silvia Consalvi
    • 1
  • Valentina Saccone
    • 1
  • Lorenzo Giordani
    • 1
  • Giulia Minetti
    • 1
    • 2
  • Chiara Mozzetta
    • 1
  • Pier Lorenzo Puri
    • 1
    • 3
  1. 1.Dulbecco Telethon Institute (DTI), IRCCS Fondazione Santa Lucia, and European Brain Research InstituteRomeItaly
  2. 2.Novartis Institutes for Biomedical ResearchBaselSwitzerland
  3. 3.Sanford-Burnham Institute for Medical ResearchLa JollaUSA

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