Update on Therapy for Myotonic Dystrophy Type 1

Purpose of review This review aimed to summarize the clinical characteristics of myotonic dystrophy type 1 and to provide a comprehensive review of the current management options for DM1 patients. Recent findings Tremendous advances in understanding the molecular pathophysiology of the disease have led to the first successful preclinical or even clinical studies of disease-modifying therapies. Repurposed small molecules, such are metformin and tideglusib, are probably closest to receiving market authorization, although they showed limited clinical efficiency in treated patients. In the last decade, different synthetic therapeutic oligonucleotides (STO) able to degrade toxic DMPK mRNA were successfully tested in DM1 preclinical studies. Following the failure of the first clinical trial of an STO in DM1 due to poor peripheral drug biodistribution, clinical studies of two other STOs, namely, AOC 1001 and DYNE-101, have been initiated in the past 2 years. Preliminary results revealed successful drug delivery to the targeted tissues with significant clinical efficacy and a satisfactory safety profile. Furthermore, promising preclinical results have been disclosed for CRISPR-based genetic modifying therapy. Summary As there is currently no approved disease-specific therapy, a multidisciplinary approach and symptomatic therapy following recently proposed consensus-based care recommendations remain the pillars of good clinical practice managing DM1 patients. Nevertheless, significant breakthroughs in the field of oligonucleotide-based and gene therapy herald the exciting times of great potential for introducing the first causal therapy targeting the genetic cause of DM1.