Histone Deacetylase Inhibitors: a Potential Epigenetic Treatment for Duchenne Muscular Dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a life-threatening genetic disease that currently has no available cure. A number of pharmacological strategies that aim to target events downstream of the genetic defect are currently under clinical investigation, and some of these are outlined in this report. In particular, we focus on the ability of histone deacetylase inhibitors to promote muscle regeneration and prevent the fibro-adipogenic degeneration of dystrophic mice. We describe the rationale behind the translation of histone deacetylase inhibitors into a clinical approach, which inspired the first clinical trial with an epigenetic drug as a potential therapeutic option for DMD patients.

Keywords::

• chromatin
• epigenetics
• HDAC inhibitors
• muscular dystrophy
• muscle stem cells
• regeneration

Acknowledgements

The authors would like to thank PL Puri for his invaluable sustainability and mentorship.

Financial & competing interests disclosure

S Consalvi and V Saccone have a patent pending approval, with no royalties, in conjunction with Italfarmaco, the sponsor of the Phase I/II clinical trial with givinostat in the treatment of Duchenne muscular dystrophy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

S Consalvi and V Saccone have a patent pending approval, with no royalties, in conjunction with Italfarmaco, the sponsor of the Phase I/II clinical trial with givinostat in the treatment of Duchenne muscular dystrophy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.