The 65-year-old is one of six people in the world to receive gene therapy for a rare type of inherited eye disease called choroideremia. The first published results of the trial, released today, suggest that tinkering with people’s genes can stop the disease from causing blindness – and restore sight in those whose vision has become impaired.
The results could eventually be relevant to the treatment of a much more common cause of blindness, age-related macular degeneration, which is caused by whole host of faulty genes. Even more broadly, the positive results are part of a recent trend in gene therapy success, following a shaky start more than 20 years ago.
Choroideremia is caused by defects in the CHM gene, which produces a protein called REP-1 and affects one in 50,000 people. In those who have the disease, a lack of REP-1 means that cells in the retina stop working and slowly begin to die off, causing blindness. When he was in his twenties, doctors told Wyatt that he would be blind by the time he was 50 – and that there was no cure.
Neurons for life
Enter gene therapy, which uses a vector – usually a virus – to insert a functioning copy of a gene into cells with a gene defect and could in principle be used to treat many genetic conditions. Robert MacLaren of the University of Oxford and his colleagues decided to see if it could correct choroideremia.
Starting two years ago with Wyatt, they injected a virus carrying a corrective copy of the CHM gene into the retinas of people with choroideremia.
Today the team reports that of the six people who received the treatment six months ago or longer, all have described improvements in their vision. “The very next day I saw a mobile phone and I said ‘I can read the digits!’ I hadn’t been able to read the digits on a mobile phone for five years,” says Wyatt.
All the people in this trial had varying levels of degeneration before the treatment. However, MacLaren is hopeful that the therapy could also be used to stop choroideremia before there is any significant loss of vision.
It’s not the first time gene therapy has been used to improve vision: it has also been used to restore vision in people with the retinal disease Leber’s congenital amaurosisMovie Camera, for example. However, in this case the target cells were pigment ones, which eventually die off to be replaced by new ones. By contrast, the MacLaren team’s therapy targets photoreceptors that are neurons lasting for life – so in principle patients need only have the treatment once.
Still, the long-lasting effects of the treatment remain unknown. Wyatt had the treatment first, so can reveal that the benefits seem to last two years, but he’s just one case.
“Given the relatively slow degeneration in this condition, longer-term studies will be required,” says James Bainbridge of the Institute of Ophthalmology at University College London.
The treatment also can’t replace cells that have been completely destroyed. “We’re trying to rescue the cells that are there already, to return the function of those cells to normal,” says MacLaren. “What we can’t do is bring back the cells that have already gone. That’s one of the distinguishing features between stem cell therapy, which is to regenerate lost tissue, and gene therapy, which at the moment is there to sustain cells that would otherwise die.”
MacLaren’s work is part of a broader trend in the success of gene therapy, which got off to a bad start. The first people to be treated with a gene therapy had ADA-SCID, also called “bubble boy disease”, and some later got leukaemia, probably because the virus carrying the new genes also switched on cancer genes.
Specifically, the new results boost knowledge about the effects of the viral vector used, adeno-associated virus, which has been successfully used in gene therapy for the eye since 2008. “The early results of this clinical trial add to the expanding body of experience on the safety of AAV vectors in the eye,” says Bainbridge.
Source: New Scientist website