PEOPLE with muscular dystrophy have been given fresh hope by gene therapy experiments that have successfully treated the mouse equivalent of the disease. Mouse muscles disabled by the condition started working again after a single treatment.
The researchers who made the breakthrough hope that the approach will also work in human patients with Duchenne muscular dystrophy, a muscle-wasting disease that afflicts 1 in 3000 boys. The muscles of patients gradually wither because they have a faulty gene for making dystrophin, a vital protein that gives muscle cells their shape and strength.
There is no cure. Attempts to treat the condition with gene therapy supplying new, functioning copies of the gene faltered when patients reacted to the viruses used to deliver the genes to the muscle cells. Even when delivered, the new genes failed to work satisfactorily, or reached too few muscles to make any difference. Attempts to treat the condition with donated stem cells in the hope they would grow into healthy muscle have been equally disappointing.
Advertisement
Qi Long Lu and his colleagues at Hammersmith Hospital in London tried a new tack. They aimed to make the patient鈥檚 own faulty dystrophin gene work properly.
Rather than trying to replace the whole gene, they decided to 鈥渆dit out鈥� the mistake, which normally cuts short the production of the dystrophin protein. Lu designed a short piece of RNA that would bind to the faulty region in each cell鈥檚 RNA copies of the dystrophin gene. When he injected it into the muscles of mice with the disease, it bound to the dystrophin RNA, masking the error so that it was skipped over and the protein was successfully produced. The animals鈥� muscles started working again and were still working up to 3 months after the injections.
Lu says the same type of fault causes most cases of muscular dystrophy in humans, so the RNA molecule could be tailored to recognise specific mutations. 鈥淵ou could customise it for each patient,鈥� he says. His results have been published online in Nature Medicine (DOI: ).
But before he tries it in humans, Lu wants to try injecting the preparation into the mice鈥檚 blood. This would be more effective than injections into individual muscles, as blood would deliver the RNA to muscles all over the body.