Gene therapy for Duchenne muscular dystrophy: balancing good science, marginal efficacy, high emotions and excessive cost

Duchenne muscular dystrophy (DMD), the most common form of all muscular dystrophies, is an X-linked disorder affecting approximately one in 5000 newborn boys.1 Patients experience difficulty in ambulation which steadily progresses to wheelchair confinement by the age of 12 and death between 25–30 years of age due to respiratory muscle weakness or cardiomyopathy. DMD is caused by mutations in the dystrophin gene, with 65% being deletions (the rest duplications or point mutations) that disrupt the open-reading frame of dystrophin mRNA, preventing the expression of a functional protein.1,2 Lack of dystrophin, a structural sarcolemmal protein that stabilizes the muscle fibre, causes muscle fibre degeneration, inflammation and fibrosis, clinically manifested as muscle weakness.2