Researchers have overcome one of the major hurdles in using gene therapy to treat muscle diseases: delivery of the gene to muscles throughout the body. The study, to be published in the journal Nature Medicine next month, is further progress towards treating diseases such as Duchenne muscular dystrophy (DMD), which is the most common lethal childhood genetic disease.
Muscular dystrophy is the generic name for a group of diseases that are caused by faults in a gene known as dystrophin. Gene therapy has previously been used to treat muscular dystrophies, by injecting viruses carrying the gene directly into muscle, but the latest research uses the bloodstream to deliver the gene to muscles throughout the body.
The research team, based at the University of Washington (US), conducted experiments on mice lacking the dystrophin gene, which exhibit similar symptoms to DMD sufferers. The team were able to reverse these symptoms by delivering a copy of the gene using a particular type of virus. This virus, called adeno-associated virus (AAV) pseudotype 6, is able to target muscle cells, so the gene is only delivered to those cells that need it. As the virus is unable to replicate on its own, it poses little risk to humans.
The naturally occurring form of the dystrophin gene is too large to fit inside a virus, so the researchers had to use a scaled down version, known as micro-dystrophin. In a further use of clever science, the team combined the gene therapy with drugs that increased the permeability of the blood vessels, allowing the viruses to leave the bloodstream and deliver the gene to the muscle.
'By giving one single injection of this AAV carrying a dystrophin gene into the bloodstream, we are able to deliver therapeutic levels of dystrophin to every skeletal and cardiac muscle of an adult, dystrophic mouse', said Professor Jeffery Chamberlain, leader of the research team. Chamberlain, director of the University of Washington's Muscular Dystrophy Co-operative Research Centre, is currently putting together a proposal for a trial of this procedure in humans. Despite saying that further work on animals was needed, he expressed hopes of full-scale human trials in five years with widespread use in ten.
Although developed with muscular dystrophy in mind, the technique should allow delivery of a wide variety of genes to the muscle. This means it has wide-ranging potential to treat muscular ailments, but raises further questions about the use of genes for cheating in sport. Chamberlain shrugs off these fears saying, 'it would be really easy to detect because the adeno-associated virus would stay around for years in the body'.