Therapeutic approach for myotonic dystrophy: Recent advances in translational research

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults, caused by unstable genomic expansions of CTG or CCTG repeats. Mutant RNA transcripts containing expanded repeats form ribonuclear foci and cause a toxic gain-of-function by perturbing splicing factors in the nucleus, resulting in misregulation of alternative pre-mRNA splicing, known as “spliceopathy.” The misregulated splicing is thought to be responsible for multisystemic symptoms in DM. Although no curative treatment exists, recent advances in basic and translational research provide clues on therapeutic interventions for DM. Here, the RNA-mediated molecular pathomechamism and therapeutic approaches targeting the toxic RNA with antisense oligonucleotides and small molecules are reviewed.