Encouraging results from exon skipping gene-based therapy study for DMD

Scientists at Royal Holloway, University of London have reported encouraging results in a new gene-based therapy for Duchenne Muscular dystrophy (DMD) which at present has no known cure and affects one in 3,000 young boys.

All the muscular dystrophies are caused by faults in genes passed on by parents to their children and they cause progressive muscle weakness because muscle cells break down and are gradually lost. The Duchenne type affects only boys and those affected develop the first signs of difficulty in walking at the age of one to three years.

The research, led by Professor George Dickson from the School of Biological Sciences at Royal Holloway, involved a new genetic therapy called exon skipping, which was tested in an experimental model of the debilitating muscle disease. As a result of the treatment there was a remarkable and long-term improvement in the symptoms of the disease.

Exon skipping is a gene therapy approach that is currently in clinical trial for DMD and involves short strands of synthetic DNA known as an 'antisense oligonucleotide' which can be considered a sort of 'molecular patches'. The treatment can restore production of the protein dystrophin (which is missing in boys with DMD) and works by masking the faulty part of the dystrophin gene, allowing a shortened but functional dystrophin protein to be produced. It is thought that this method could potentially transform the symptoms of the severe Duchenne form of muscular dystrophy to those akin to the much milder so-called 'Becker' muscular dystrophy.

This study provides further evidence of the potential of this technique for treating DMD. There are currently clinical trials in progress in the UK and the Netherlands testing slightly different forms of the molecular patches which are producing promising initial results. Professor Dickson commented, "Duchenne dystrophy is very serious inherited disorder which affects 1 in 3,000 boys from age four onwards. It is a progressive and severe muscle wasting disease which is currently untreatable. These latest exciting and encouraging results suggest that current ongoing clinical trials of exon skipping in muscular dystrophy patients have great promise as a long-term treatment."

The research, published in Molecular Therapy, is part-funded by the Muscular Dystrophy Campaign. Director of Research at the Muscular Dystrophy Campaign, Dr Marita Pohlschmidt said: "Finding the right dose of this new potential drug is key to its success and we are proud that the research we fund continues to shed light on this. Professor Dickson's work has provided us with a good indication of what dose might be effective to improve muscle function in boys with Duchenne muscular dystrophy and we hope that these results are confirmed in clinical trials."