title: Applicability of histone deacetylase inhibition for the treatment of spinal muscular atrophy.
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.
authors.affiliation: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, 3004, Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lunke
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases