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RNA-mediated therapies in myotonic dystrophy. | LitMetric

RNA-mediated therapies in myotonic dystrophy.

Drug Discov Today

University of Valencia, Interdisciplinary Research Structure for Biotechnology and Biomedicine (ERI BIOTECMED), Valencia, Spain; Translational Genomics Group, Incliva Health Research Institute, Valencia, Spain; Joint Unit Incliva-CIPF, Valencia, Spain. Electronic address:

Published: December 2018

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.

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http://dx.doi.org/10.1016/j.drudis.2018.08.004DOI Listing

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