Gene therapy for spinal muscular atrophy could be tested in 2 years
Gene therapy for spinal muscular atrophy could be tested in 2 years
A new treatment for an incurable wasting disease that kills about 50 British infants every year could begin human trials within two years, after highly encouraging results in animals.
The gene therapy for spinal muscular atrophy (SMA), which aims to correct the faulty DNA that causes the condition, has dramatically prolonged the lives of mice with the mutation, while improving their nerve and muscle function. The treated rodents lived for more than 250 days, which is five times longer than those given any other type of therapy and 16 times longer than untreated animals.
A version of the therapy has also been successfully tested on a monkey, suggesting that the technique is highly likely to work in human beings.
Scientists at Ohio State University, who conducted the study, will apply to start trials on children as soon as they have finished toxicity testing. They hope to treat the first patients within two years.
If human studies are successful, the gene therapy could transform the treatment of SMA, which affects up to one in 6,000 babies.
The condition occurs when two mutant genes are inherited, one from each parent, impairing production of a protein called SMN. The deficiency disables patients by killing critical cells in the spinal cord.
The most serious form affects infants, who are so severely paralysed that they cannot lift their heads. They generally die of respiratory failure by their second birthdays. Other types can cause childhood paralysis and breathing difficulties, or impair movement in adolescence or adulthood. While symptoms can sometimes be managed with physical therapy and drugs, there is no cure.
The gene therapy, details of which are published in the journal Nature Biotechnology, uses a modified virus to correct the faulty gene and restart SMN production. It was injected into newborn mice, restoring nerve and muscle function and prolonging their lifespans.
“We’re replacing what we know is lost,” said Arthur Burghes, a leader of the study. “This technique corrects the mice considerably more than any drug cocktails being studied as a potential treatment in humans.”
The viral vector for the therapy was also used to carry a different gene into monkeys, showing that it can get DNA into the nervous system. This bodes well for human trials, though several barriers still remain.
Scientists must establish that the treatment is not toxic, and how soon after birth it must be given to stand a chance of success. The US Food and Drug Administration will also have to approve a trial. Clinical use would require screening of newborns, so that children can start treatment early.
Dame Kay Davies, Professor of Anatomy at the University of Oxford, who led the team that identified the defective gene causing SMA, said: “This is very promising, a very good proof of principle which suggests it is now worth trying in Man. It is an illustration of how far gene therapy has come.”
Alex MacKenzie, a SMA researcher at the University of Ottawa in Canada, said: “This study, combined with the possibility of disease screening in newborns, raises, for the first time, hope of real therapeutic progress against this as yet untreatable disorder.”