Myotonic Dystrophy Type 1: A Comprehensive Literary Review

Abstract

Myotonic Dystrophy Type 1 (DM1) is a degenerative neuromuscular disease that costs 448 million dollars in the US annually to combat. Caused by the abnormal expansion of the CTG sequence located along the Dystrophia Myotonica Protein Kinase (DMPK) gene of chromosome 19, DM1 results in several different observable effects that include, but are not limited to cataracts, facial weakness, hypersomnia, cardiomyopathy, and arrhythmias. Symptoms are attributed to the rapid degeneration of muscles that leads to weakened control over the heart, lungs, gastrointestinal systems, and face. Treatments for DM1 are limited to minimizing morbidity such as through assistive mobility devices. In pursuit of a cure, pre-clinical models have provided a foundation for deeper investigations into the pathogenesis of DM1. Ongoing studies utilize molecular genetics and pharmacology to target the underlying molecular mechanisms, fortunately, many of these studies have shown potential in pre-clinical trials. Antisense therapy targets expanded trinucleotide regions and has demonstrated recovery of cardiac muscle in mice. CRISPR/SpCas9, when injected, has shown beneficial effects in several DM1 animal models. Furthermore, given the pre-clinical success of the novel pharmacologic agent AOC 1001, clinical trials have been initiated and are ongoing. Unfortunately, due to the nuances and difficulties in treating DM1, there is currently no Food and Drug Administration-approved disease-modifying therapies, and as such DM1 represents a growing public health concern.