title: [Myotonic dystrophy: therapeutic approaches to RNA toxicity].
abstract: Myotonic dystrophy (DM) is the most common hereditary muscle disease in adults, caused by unstable genomic expansions of simple sequence repeats. The mutant RNA transcripts containing the expanded repeat give rise to a toxic gainoffunction by perturbing splicing factors in the nucleus, leading to the misregulation of alternative pre-mRNA splicing. Although no curative treatment exists, recent advances in research and pharmaceutical technology have provided clues for therapeutic intervention in DM. Herein, we review the RNA-dominant mechanism of DM and potential therapeutic approaches for degrading or neutralizing the toxic RNA, restoring splicing factors, correcting splicing misregulation, and stabilizing the repeat.
authors: Department of Neurology, Osaka University Graduate School of Medicine, Suida, Osaka, Japan.
authors: Masayuki
authors: M
authors: Nakamori
authors: Masanori P
authors: MP
authors: Takahashi
mesh_terms: D000818:Animals; D000067879:CELF1 Protein; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000628:therapy*; D012313:RNA / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D000067879:CELF1 Protein; C102843:CELF1 protein, human; C493663:MBNL1 protein, human; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D012313:RNA