Gene therapy partially restores vision in rare blindness disorder


Two men with progressive blindness have regained some of their vision after taking part in the first clinical trial of a gene therapy for the condition.

The men were among six patients to have experimental treatment for a rare, inherited, disorder called choroideremia, which steadily destroys eyesight and leaves people blind in middle age.

After therapy to correct a faulty gene, the men could read two to four more lines on an optician’s sight chart, a dramatic improvement that has held since the doctors treated them. One man was treated more than two years ago.

The other four patients, who had less advanced disease and good eyesight before the trial, had better night vision after the therapy. Poor sight in dim light is one of the first signs of the condition.

Writing in The Lancet , doctors describe the progress of the patients six months after the therapy. If further trials are as effective, the team could apply for approval for the therapy in the next five years. Some other forms of blindness could be treated in a similar way.

Toby Stroh, 56, a solicitor from London, was in his early 20s when a consultant told him he would be blind by the age of 50. “I said ‘what do you mean?’ and he said, ‘you won’t be able to see me’. It was a long way away, but still a bit of a shock.”

Stroh was told later that his vision had deteriorated so much he would have to stop driving. Then, when he joined a solicitors’ firm he told a partner his eyesight was not expected to last. The response was: “We’ll be sorry to see you go.”

Stroh had gene therapy to his left eye, the worst eye, in February 2012, and has had some sight return to it.

“This result does not make me swing from the chandeliers. I refuse to say everything is going to be roses. But there is hope,” he said. “For the past 30 years I’ve been living under the awfulness, the insidious inevitability, of going blind, and now as a result of this work that’s been done there is a very real prospect that I will continue to be able to see, and that is just absolutely fantastic.”

Jonathan Wyatt, 65, a barrister from Bristol, was the first patient to have the therapy. He had hoped to spend his youth surfing around the world, but changed his mind at the age of 20 when a consultant told him he had no idea if his vision would last one, two or three more years.

Wyatt had gene therapy in October 2011 and soon after was able to read the numbers on a mobile phone for the first time in five years. “In my view my eyesight has improved enormously since the operation.”

Doctors said the improvements in the two patients went far beyond their expectations, but they cautioned that it was too soon to say whether the effects would last.

“It is still too early to know if the treatment we have initiated is a permanent cure, but so far the vision that we’ve seen improved has been maintained,” said Robert MacLaren, a consultant surgeon at the Oxford Eye Hospital, who led the trial.

Choroideremia is an X-linked disorder, meaning it is caused by a faulty gene, called CHM, on the X chromosome. The disease mostly affects men because they have only one copy of the X chromosome. Women have two copies of the X chromosome, so a healthy version of the gene on one chromosome can largely make up for any defects on the other.

The therapy uses a genetically modified virus to smuggle healthy copies of the CHM gene into light-sensitive cells in the retina and supporting tissue called retinal pigment epithelium.

Surgeons injected 10bn modified virus particles behind the retinas of the first six patients in an operation that could be completed in an hour under general anaesthetic.

The injected viruses infect the eye cells, which then use the new CHM gene to correct the choroideremia. The therapy only works on cells that have not been destroyed by the disease. It cannot replace cells that have died off.

MacLaren has given three more patients a higher dose of the gene therapy and hopes to start a larger trial with about 30 people next year.

Wayne Thompson, 43, an IT manager in Staffordshire, was treated in April 2013. His night vision began to fail in his 20s, and over time his peripheral vision got worse, until he began to use a white cane to get around.

“One night in the summer my wife called me outside as it was a particularly starry evening. As I looked up I was amazed that I was able to see a few stars. I hadn’t seen stars for a long, long, time,” Thompson said. “Even if the improvement lasts I will still be visually impaired. My life has not become easier because of the trial, but it may have stopped it getting much, much, harder.”

The work raises hopes for gene therapies for more common causes of blindness, such as retinitis pigmentosa and age-related macular degeneration. Some forms of blindness cause rapid sight loss, and are caused by multiple genes, so therapy might need to be given in childhood and correct several genes at once.

“It’s pretty convincing that they see some functional improvement in the treated eyes,” said Hendrik Scholl, professor of ophthalmology at Johns Hopkins University. “I find this very exciting.”

But he added that measurements of supporting tissues, called retinal pigment epithelial cells, seemed to show that the therapy had not stopped the degeneration of the eye completely. “The data suggest that they were able to slow down the progression of the disease, but not stop it. But after only six months it is very difficult to draw any conclusions.”

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