Developing drugs to treat myotonic dystrophy

Developing drugs to treat myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults.  It is a highly debilitating condition with an average life expectancy of 58 years, affecting more than 100,000 patients in developed countries.  DM1 is primarily a neuromuscular disorder, which also affects a range of other systems including the heart, brain, endocrine and digestive systems.  Patients may also show psychological dysfunction, cognitive impairment and excessive daytime sleepiness.  There is no treatment for DM1 and all features show an obvious deterioration with time.

DM1 is caused by a repeat expansion mutation in the 3’ untranslated region of the DMPK gene.  Unaffected people have 5 to 30 copies of a CTG sequence whereas patients may have hundreds or sometimes thousands of copies.  When expressed the DMPK expansion transcripts remain in the nucleus where they form distinct spots or foci.  Professors Chris Hayes and David Brook at the University of Nottingham developed an assay to screen for compounds that might provide a treatment for DM1.  They identified small molecules that target a novel protein and destroy the spots in DM1 cells, thereby leading to a significant reduction in the faulty RNA and other molecular features of the disorder.  This Seeding Drug Discovery award, in collaboration with Argenta Discovery, is based on targeting this novel protein, by generating unique molecules that are selective and more suitable for oral administration to patients.  Professors Hayes and Brook anticipate that a successful drug would target most/all features of the disease.