In this project Professor Wells and his PhD student will investigate ways to improve the delivery of molecular patches so they can reach all the muscles more easily. Molecular patches are currently in clinical trial for Duchenne muscular dystrophy, but researchers face a challenge in trying to get enough of the patches to all the muscles in the body.
What are the researchers aiming to do?
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene. This gene contains the instructions for making dystrophin protein which acts as a shock absorber to prevent damage when the muscle contracts. The loss of dystrophin in Duchenne muscular dystrophy leads to wasting of the muscle, with the muscle fibres gradually being replaced by fat and scar tissue.
Exon skipping is currently in clinical trial as a potential treatment for Duchenne muscular dystrophy. It involves using small pieces of DNA called molecular patches or ‘antisense oligonucleotides’ to change the way the instructions contained within a gene are read. This has the effect of restoring the production of dystrophin protein. It is thought that the molecular patches will change the symptoms of Duchenne muscular dystrophy into those akin to the milder Becker muscular dystrophy.
It is proving to be a challenge, however, for sufficient amounts of the molecular patches to travel from the blood stream where they are injected, into all the muscles of the body and particularly the heart. This project aims to investigate ways of making the blood vessels more “leaky” so that more molecular patch is able to pass from the blood stream into muscles.
How will the outcomes of the research benefit patients?
Exon skipping has already shown some promise in clinical trial, but the results have suggested that improvements in delivery are needed to get the best possible results. Improving the delivery of the molecular patches has the potential to vastly improve the effectiveness of exon skipping giving greater improvement in muscle strength and function. It may also allow the use of lower doses of molecular patch which may be safer and cheaper.
This research could also benefit people with other neuromuscular conditions such as myotonic dystrophy that affect the heart and for which similar molecular patch technology is showing promise as a potential therapy.
Project leader: Prof Dominic Wells
Location: Royal Veterinary College, London
Conditions: Duchenne muscular dystrophy
Duration: 4 years, starting 2012
Total project cost: £113,810
Official title: Improving vascular delivery of antisense oligonucleotides to striated muscle in vivo
Find out more about exon skipping
Read about other Duchenne muscular dystrophy research into we fund
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