title: Manumycin A corrects aberrant splicing of Clcn1 in myotonic dystrophy type 1 (DM1) mice.
abstract: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults and as yet no cure for DM1. Here, we report the potential of manumycin A for a novel DM1 therapeutic reagent. DM1 is caused by expansion of CTG repeat. Mutant transcripts containing expanded CUG repeats lead to aberrant regulation of alternative splicing. Myotonia (delayed muscle relaxation) is the most commonly observed symptom in DM1 patients and is caused by aberrant splicing of the skeletal muscle chloride channel (CLCN1) gene. Identification of small-molecule compounds that correct aberrant splicing in DM1 is attracting much attention as a way of improving understanding of the mechanism of DM1 pathology and improving treatment of DM1 patients. In this study, we generated a reporter screening system and searched for small-molecule compounds. We found that manumycin A corrects aberrant splicing of Clcn1 in cell and mouse models of DM1.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Oana
authors.forename: Yoko
authors.initials: Y
authors.lastname: Oma
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suo
authors.forename: Masanori P
authors.initials: MP
authors.lastname: Takahashi
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels / Q000235:genetics*; D017931:DNA Primers; D051379:Mice; D009223:Myotonic Dystrophy / Q000235:genetics*; D011090:Polyenes / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D012326:RNA Splicing / Q000187:drug effects*
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D017931:DNA Primers; D011090:Polyenes; D053284:Polyunsaturated Alkamides; C054474:manumycin