New Perspectives in the Management of Duchenne Muscular Dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked, rare, progressive, life-threatening disease with no currently approved therapy targeting the underlying cause. DMD is characterised by a lack of dystrophin, which leads to severe myofibre degeneration. Laboratory techniques have evolved to enable identification of DMD patients from blood samples. The importance of a multi-disciplinary clinical management approach in achieving optimal outcomes in DMD is well recognised, and there is an emphasis on utilising care guidelines to treat effectively the multiple clinical manifestations of DMD. The aim of managing DMD is to prolong ambulation and delay other disease milestones, therefore maintaining quality of life for as long as possible. In the absence of any other approved treatments, corticosteroids have been adopted as a standard of treatment for DMD, with evidence supporting their clinical utility in delaying some disease milestones, while recognising their side effects. A major challenge with DMD has been the identification of meaningful clinical outcome measures for clinical studies. The 6-minute walk test (6MWT) has emerged as a strong predictor of physical functioning and disease progression, with strong evidence of validity and reliability. As a result, it is currently the most accepted primary clinical endpoint in ambulatory DMD clinical trials. The 6MWT has been utilised in a variety of DMD studies of potential drug treatments, including large multinational trials of the nonsense mutation readthrough agent, ataluren, which is under development for nonsense mutation-mediated DMD, in trials of exon skipping agents in development for specific exon linked DMD mutations and in trials investigating optimal steroid dose regimens.