title: Myotonic dystrophy: approach to therapy.
abstract: Myotonic dystrophy (DM) is a dominantly-inherited genetic disorder affecting skeletal muscle, heart, brain, and other organs. DM type 1 is caused by expansion of a CTG triplet repeat in DMPK, whereas DM type 2 is caused by expansion of a CCTG tetramer repeat in CNBP. In both cases the DM mutations lead to expression of dominant-acting RNAs. Studies of RNA toxicity have now revealed novel mechanisms and new therapeutic targets. Preclinical data have suggested that RNA dominance is responsive to therapeutic intervention and that DM therapy can be approached at several different levels. Here we review recent efforts to alleviate RNA toxicity in DM.
authors.affiliation: Department of Neurology, University of Rochester, Rochester 14642, NY, United States. Electronic address: charles_thornton@urmc.rochester.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Thornton
authors.affiliation: Department of Molecular Genetics & Microbiology, Center for NeuroGenetics, University of Florida, Gainesville, FL, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of Rochester, Rochester 14642, NY, United States.
authors.forename: Ellie M
authors.initials: EM
authors.lastname: Carrell
mesh_terms: D005786:Gene Expression Regulation / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D065636:Myotonin-Protein Kinase / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics* / Q000627:therapeutic use; D016601:RNA-Binding Proteins / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C433227:CNBP protein, human; C585517:DMPK protein, human; D016372:RNA, Antisense; D016601:RNA-Binding Proteins; D065636:Myotonin-Protein Kinase