6533b828fe1ef96bd12884c9

RESEARCH PRODUCT

RNA-mediated therapies in myotonic dystrophy

Sarah Joann OverbyRuben ArteroEstefanía Cerro-herrerosBeatriz Llamusi

subject

musculoskeletal diseases0301 basic medicinePharmacologycongenital hereditary and neonatal diseases and abnormalitiesMessenger RNAMyotonin-protein kinaseRNABiologymedicine.diseaseMyotoniaMyotonic dystrophyMyotonin-Protein KinaseCell biology03 medical and health sciences030104 developmental biologyDrug DiscoverymedicineAnimalsHumansMyotonic DystrophyRNARNA MessengerTrinucleotide repeat expansionGeneLoss function

description

Myotonic dystrophy 1 (DM1) is a multisystemic neuromuscular disease caused by a dominantly inherited 'CTG' repeat expansion in the gene encoding DM Protein Kinase (DMPK). The repeats are transcribed into mRNA, which forms hairpins and binds with high affinity to the Muscleblind-like (MBNL) family of proteins, sequestering them from their normal function. The loss of function of MBNL proteins causes numerous downstream effects, primarily the appearance of nuclear foci, mis-splicing, and ultimately myotonia and other clinical symptoms. Antisense and other RNA-mediated technologies have been applied to target toxic-repeat mRNA transcripts to restore MBNL protein function in DM1 models, such as cells and mice, and in humans. This technique has had promising results in DM1 therapeutics by alleviating pathogenic phenotypes.

yearjournalcountryeditionlanguage
2018-12-01Drug Discovery Today
https://doi.org/10.1016/j.drudis.2018.08.004