Posted on 28/11/2012
A team of scientists from several European countries and the USA, the MDEX Consortium, led by UCL scientist Prof Francesco Muntoni, Institute of Child Health and including Professor George Dickson from Royal Holloway’s School of Biological Sciences, have won an EU Health Innovation-1 2012 Collaborative research grant of €5.5 million to perform a clinical trial to test a novel drug treatment in Duchenne muscular dystrophy (DMD) boys. The work would not be possible without the involvement of Sarepta Therapeutics, Cambridge, MA, USA; who are not only providing the drug, but also half of the drug production and pre-and clinical trial costs.
DMD is a devastating and life-limiting X-linked condition that affects one in ~3,500 male births in the general population, with around 100 new cases diagnosed in the UK each year. The condition leads to progressive muscle weakness due to the breakdown and loss of muscle cells. Patients lack a single important protein in their muscle fibres called dystrophin. By the age eight to 12, boys become unable to walk and by their late teens or early twenties the condition can become severe enough to limit life expectancy.
The award follows on from an MDEX Lancet paper in July 2011, announcing that a drug known as an ‘antisense oligonucleotide’, could be used safely to restore dystrophin production in a subset of DMD boys, by ‘skipping’ one exon (in this case exon 51). However, different antisense oligonucleotides are required to skip different exons and so a panel of such drugs is required to ensure as many boys as possible can be treated. In theory, this approach could work for at least 70% of DMD sufferers. However, further research to test this proof-of-principle, is required first. To achieve this, clinical trials will be repeated in DMD boys carrying different mutations, thus requiring different exons to be skipped. The awarded grant will do just that; in this instance by skipping exon 53. Initially a safety assessment of a lead antisense oligonucleotide to skip exon 53 will be performed, followed by a randomized clinical study looking at safety, biochemical efficacy and exploratory clinical efficacy of this novel antisense in ambulant boys affected by DMD. Exploratory measures including muscle magnetic resonance imaging (MRI) and serum biomarkers will also be studied to assess non-invasively response to therapy.
Professor Dickson commented “Royal Holloway’s role is to lead a team effort to design and optimise the new therapeutic exon skipping drug, and we are very excited to contribute our expertise, and be involved with this excellent consortium of clinicians, scientists and industry partners who will perform these clinical trials in DMD patients.”