Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing

Int J Mol Sci. 2022 Apr 21;23(9):4622. doi: 10.3390/ijms23094622.

Abstract

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy affecting many different body tissues, predominantly skeletal and cardiac muscles and the central nervous system. The expansion of CTG repeats in the DM1 protein-kinase (DMPK) gene is the genetic cause of the disease. The pathogenetic mechanisms are mainly mediated by the production of a toxic expanded CUG transcript from the DMPK gene. With the availability of new knowledge, disease models, and technical tools, much progress has been made in the discovery of altered pathways and in the potential of therapeutic intervention, making the path to the clinic a closer reality. In this review, we describe and discuss the molecular therapeutic strategies for DM1, which are designed to directly target the CTG genomic tract, the expanded CUG transcript or downstream signaling molecules.

Keywords: DM1 mice; antisense oligonucleotides; gene editing; molecular therapy; myotonic dystrophy; trinucleotide-expansion disease.

Publication types

  • Review

MeSH terms

  • Gene Editing
  • Humans
  • Myotonic Dystrophy* / drug therapy
  • Myotonic Dystrophy* / genetics
  • Myotonin-Protein Kinase / genetics
  • Myotonin-Protein Kinase / metabolism
  • Trinucleotide Repeat Expansion / genetics

Substances

  • Myotonin-Protein Kinase