New perspectives on the diagnosis and management of duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disorder that occurs in around one in 5,000 male births. The prevalence of DMD is expected to rise due to improved standards of care and implementation of guidelines, leading to longer survival. Specialist genetic confirmation of a DMD diagnosis is typically followed by access to specialist care and treatment: the exact DMD-causing mutation should be identified because it can influence prognosis and identify patients eligible for treatment. Since the majority of patients has a deletion or duplication of one or more exons (~70 %), generally multiplex ligation-dependent probe amplification suffices to identify the mutation. Exon sequencing is performed to pick up small mutations (~30 %). Greater awareness of DMD is needed among healthcare professionals to enable earlier diagnosis, which would facilitate family planning, as well as patient care and treatment. In DMD patients who are still able to walk, the 6-minute walk test (6MWT) has been shown to be a valid measure of physical functioning and a predictor of disease progression, with high inter-test reliability. In a study of the natural history of DMD, change in 6MWT of around 30 metres has been indicated to be clinically relevant and clinically meaningful. DMD patients responded to treatment as shown by the improvement in the 6MWT score in the large multinational trial of the nonsense mutation readthrough agent, ataluren (Translarna™) 40 mg/kg/day, where treatment was associated with a 31.3 metres improvement on the 6MWT distance, after 48 weeks, compared with placebo. The Translational Research in Europe–Assessment & Treatment of Neuromuscular Diseases (TREAT-NMD) network was launched to provide an infrastructure to accelerate research and therapy development, increasing collaboration, improving patient care and helping to support ‘clinical trial readiness’. As such, the TREAT-NMD registry network is well placed to support further understanding of DMD and the impact of therapies that may be used over the long term, permitting a host of research questions to be explored.