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Applicability of Histone Deacetylase Inhibition for the Treatment of Spinal Muscular Atrophy

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  • Published:
Neurotherapeutics

Abstract

Spinal muscular atrophy (SMA), a neurodegenerative disease with potentially devastating and even deadly effects on affected individuals, was first described in the late nineteenth century. Although the survival of motor neuron (SMN) gene was identified nearly 2 decades ago to be causative of the disease, neither an effective treatment nor a cure are currently available. Yet efforts are on-going to test a multitude of treatment strategies with the potential to alleviate disease symptoms in human and clinical trials. Among the most studied compounds for the treatment of SMA are histone deacetylase inhibitors. Several of these epigenetic modifiers have been shown to increase expression of the crucial SMN gene in vitro and in vivo, an effect linked to increased histone acetylation and remodeling of the chromatin landscape surrounding the SMN gene promoter. Here, we review the history and current state of use of histone deacetylase inhibitors in SMA, as well as the success of clinical trials investigating the clinical applicability of these epigenetic modifiers in SMA treatment.

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Acknowledgments

The authors acknowledge grant and fellowship support from the National Health and Medical Research Council (NHMRC) and the National Heart Foundation of Australia (NHF). S.L. was awarded a Monash Graduate Scholarship and A.E-O. is NHMRC Senior Research Fellows. Supported in part by the Victorian Government’s Operational Infrastructure Support program.

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Authors and Affiliations

  1. Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, 3004, Australia

    Sebastian Lunke & Assam El-Osta

  2. Translational Genomics Laboratory, Centre for Translational Pathology, Department of Pathology, University of Melbourne, Melbourne, VIC, 3010, Australia

    Sebastian Lunke

  3. Epigenomics Profiling Facility, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia

    Assam El-Osta

  4. Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia

    Assam El-Osta

  5. Faculty of Medicine, Monash University, Monash, VIC, Australia

    Assam El-Osta

Authors
  1. Sebastian Lunke
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  2. Assam El-Osta
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Correspondence to Assam El-Osta.

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Lunke, S., El-Osta, A. Applicability of Histone Deacetylase Inhibition for the Treatment of Spinal Muscular Atrophy. Neurotherapeutics 10, 677–687 (2013). https://doi.org/10.1007/s13311-013-0209-2

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  • DOI: https://doi.org/10.1007/s13311-013-0209-2

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