25 July 2011

First Targeted Treatment Success for Duchenne Muscular Dystrophy

Scientists part-funded by the Medical Research Council (MRC) have made an important breakthrough in the development of a treatment for Duchenne Muscular Dystrophy (DMD), a devastating disease which affects around 100 boys born each year in the UK. The research was led by scientists at the UCL Institute of Child Health (ICH) and co-funded by AVI BioPharma.

The research group showed that a gene-based drug treatment called AVI-4658 was effective in raising levels of dystrophin, a key muscle protein missing in sufferers of DMD, in seven out of 19 trial participants aged five to 15 years. The treatment was administered at Great Ormond Street Hospital and the Royal Victoria Infirmary, Newcastle. AVI-4658 works by blocking a section of mutated DNA involved in around 13 per cent cases of DMD, although different mutations can also cause the disease. The scientists suggest that the treatment tested in this trial could be used to treat some boys with DMD, and that overall, the approach could work for at least 70 per cent of sufferers.

DMD is a very serious and life limiting condition, which causes progressive muscle weakness due to the breakdown and loss of muscle cells. By ages eight to 12 years boys become unable to walk, and by their late teens or early twenties the condition can become severe enough to limit life expectancy.

Professor Francesco Muntoni, who led the research from the ICH, said:

“These are very exciting results that prove the case for an even more detailed look at this genetic therapy. I’ve worked with patients with DMD for many years and this is the first time we can say with confidence that we’ve made a significant breakthrough towards finding a targeted treatment. Importantly, the study drug was extremely well tolerated, with no appreciable side effects detected during the study period in any of the boys. If our strategy shows continued success, this therapy could substantially reduced muscle damage in affected boys with DMD, improve the quality of life for DMD patients, their mobility and the way their condition is managed as they get older.”

Professor Max Parmar, director of the MRC Clinical Trials Unit, said:

“A large proportion of new drugs do not make it past the phase II stage of testing reached here, so there is real excitement that this treatment could work. This is a great example of partnership between the Medical Research Council, industry, universities and the NHS, undertaking experimental studies in the clinic with the potential to bring real benefits to patients and their families. What this encourages us to do now is conduct larger, longer term studies. These will enable us to see whether this drug, which brings expertise in genetics and chemistry together, can make a major long-term difference to the quality and length of life for boys with this devastating disease.”

The research was conducted by the MDEX Consortium, which is chaired by Professor Muntoni. The consortium aims to develop and test treatments for DMD. This study is published in The Lancet today.

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  1. The paper ‘Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study’ by S Cirak, V Arechavala-Gomeza, M Guglieri, F Muntoni et al is published in The Lancet.
  2. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk
  3. The MDEX consortium led by Professor Francesco Muntoni, is a multidisciplinary enterprise to promote translational research into muscular dystrophies, and is formed by the clinical groups of Professor Francesco Muntoni (UCL Institute of Child Health) and Professor Kate Bushby and Professor Volker Straub (Newcastle University), and scientists from The Royal Veterinary College, London (Professor Dominic Wells), UCL Institute of Child Health (Dr. Jennifer Morgan), Royal Holloway University of London (Professor George Dickson), Oxford University (Dr. Matthew Wood) and University of Western Australia (Professor Steve Wilton). In addition, the charities Muscular Dystrophy Campaign (MDC), Action Duchenne and Duchenne Family Support Group also participate in the Consortium. For more information, visit www.mdex.org.uk
  4. AVI BioPharma is focused on the discovery and development of RNA–based drugs utilizing proprietary derivatives of its antisense chemistry (phosphorodiamidate morpholino oligomers or PMOs) that can be applied to a wide range of diseases and genetic disorders through several distinct mechanisms of action. AVI’s RNA–based drug programs are being evaluated for the treatment of Duchenne muscular dystrophy with AVI-4658. AVI’s antiviral programs have demonstrated promising outcomes in Ebola Zaire and Marburg Musoke virus infections and may prove applicable to other viruses.