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

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.

Automated summary

Myotonic dystrophy type 1 (DM1) is a common muscular dystrophy that primarily affects skeletal and cardiac muscles, as well as the central nervous system. The disease is caused by the expansion of CTG repeats in the DMPK gene, leading to the production of a toxic CUG transcript. By directly targeting the CTG genomic tract, the expanded CUG transcript, or downstream signaling molecules, molecular therapeutic strategies show promise in treating DM1.