Promising new gene therapy for Duchenne Muscular Dystrophy

A potential new gene therapy for Duchenne Muscular Dystrophy (DMD) is now set to enter clinical trials after encouraging results in mice. The multinational team of scientists, publishing their findings in the journal Molecular Therapy, demonstrated that the therapy dramatically prevented severe muscle deterioration and extended the lifespan of mice with symptoms of DMD.

DMD is the most prevalent of the nine types of muscular dystrophy and indeed one of the commonest genetic disorders to affect children globally. One in 3500 boys are afflicted with this incurable disease, which results in progressive weakness and wasting of the muscles. Mobility is gradually lost, leaving most affected children wheelchair-bound before their teens, and death typically ensues before 30 years of age.

DMD is caused by a mutation in a gene found on the X chromosome which codes for a protein called dystrophin, an important structural component of muscle. Unlike males, females have 2 copies of the X chromosome and having just one normal copy of the gene is sufficient to produce enough functional protein to compensate. Women may be 'carriers' of the disease however and can pass the disease onto any sons. The new gene therapy works by masking the faulty part of the dystrophin gene. The technique, referred to as 'exon-skipping', results in a shortened but functional dystrophin protein.

Mice lacking both dystrophin and a similar protein called utrophin have a disease which closely resembles DMD. When given once weekly injections of the therapy, the treated mice had improved mobility compared to untreated mice and their limb strength was similar to normal mice. Most of the untreated mice died by 10 weeks of age, but the treated mice still appeared healthy at 26 weeks, when the study ended.

Other gene therapies for DMD, including another one based on 'exon-skipping', are already in human trial and are showing promising initial results. This new therapy however, developed by AVI BioPharma, is additionally tagged with small protein molecules called 'peptide-conjugated morpholino oligomers' (PPMOs) which improve absorption into the muscle tissue. The advantage therein is twofold: the therapy is likely to work in a greater proportion of DMD cases and improvement in symptoms and life expectancy is predicted to be even more pronounced.

'These findings, should they prove to be repeatable in human subjects, hold great promise for the treatment of DMD patients,' said the senior author of the study, Dame Kay Davis of Oxford University. 'It raises the prospect that we can make a pretty spectacular clinical difference'.