Experimental Gene Therapy Improves Sight in Patients Going Blind

Toby Stroh was in his 20s when his doctor told him he would go blind in his 50s, and his years of playing tennis and being able to drive or work could be gone long before that.

Now aged 56, two years after his retina was deliberately infected with a virus carrying a gene to correct a protein deficiency that was destroying its cells, he is a regular on the tennis court and has a successful career in law.

"For the last 30 years I've been living under the insidious inevitability of going blind," Stroh told reporters at a briefing about his experimental treatment. "Now there is a very real prospect I will continue to be able to see."

Stroh is one of a handful of patients with an inherited cause of progressive blindness called choroideremia who took part in an early stage trial of a potential gene therapy treatment designed to correct a genetic defect that means retina cells gradually die.

Although the results are from only six patients in a very early stage Phase I trial, researchers said they suggest more studies should be done to see if similar gene therapies could be developed for other more common genetic causes of blindness such as macular degeneration and retinitis pigmentosa.

Choroideremia is caused by a mutation in a gene that makes a protein called REP1. It affects an estimated 1 in 50,000 people and causes sufferers - mainly men - to lose their sight gradually as the cells in the retina degenerate.

DELIVERING DNA

There is currently no licensed treatment for the condition and eventually the photoreceptor cells - the rods and cones in the retina that respond to light by sending signals to the brain - die completely, leading to blindness by middle age.

In the trial, a team led by Robert MacLaren of the University of Oxford, a consultant surgeon at the Oxford Eye Hospital, injected the patients' retinas with a vector - in this case a genetically engineered virus - to deliver a corrective copy of the gene to the appropriate part of the eye.

"The virus has to be delivered to the target cells, which are the cells of the retina," MacLaren explained. To do that, the surgeon performs an operation similar to cataract surgery in which the patient's retina is detached and lifted, and the virus is then injected underneath with a fine needle.

"The virus goes in, infects the cells and puts the protein back into the cells - so we're harnessing the capability of the virus to infect cells and deliver its DNA," he said.

"This is the exciting thing about gene therapy," said MacLaren, whose trial results were published in The Lancet medical journal on Thursday. "We're talking about a single one-off genetic correction ... that has long-standing effects that so far have not been shown to diminish."

The results showed that of the six patients treated - each of them only in one eye so the other could act as a comparison - the two with the least good sight before the gene therapy had significantly improved vision six months later.

In the other four patients, whose vision was only slightly impaired before treatment as they were at earlier stages of the condition, the results confirmed the gene therapy is safe, with the virus delivering its DNA without damaging the retina.

"It is still too early to know if the ... treatment will last indefinitely," MacLaren said. "But we can say that the vision improvements have been maintained for as long as we have been following up the patients, which is two years in one case."

He stressed that the therapy is still in the experimental stage, with more trials likely to take up to five years before it could be submitted for a licence with a view to making it available to all patients.

"If we were able to treat people early, get them in their teens or late childhood, we'd be getting the virus in before their vision is lost," he said. "If the treatment works, we would be able to prevent them from going blind." -- © Reuters