Miracle in sight; helping the blind to see

Science in the 21st century: Miracle in sight
A cure for blindness is the breakthrough every scientist working in the field of opthalmology dreams about. Now, a team of gene therapy researchers at Moorfields Hospital may be on the brink. By Jeremy Laurance
Published: 02 May 2007
Independent UK

British scientists have claimed a world first for a new form of gene therapy that could help the blind to see.

Specialists at University College London and Moorfields Eye Hospital are testing the revolutionary treatment on 12 patients, who are aged between eight and their mid-20s, and have an inherited eye disorder.

The technique has already been shown to work in animals affected by the same disorder, called inherited retinal degeneration, and their sight was restored after treatment.

If proved successful in humans, the scientists hope the technique can be extended to other forms of eye disease that affect hundreds of thousands of people in Britain and millions around the world. Professor Robin Ali, who is leading the research, said it was "very exciting" and represented "a huge step towards establishing gene therapy for the treatment of many different eye conditions".

But the professor warned that the work was at an early stage aimed at establishing the safety and efficacy of gene transfer to the eye, and that gene therapy for many common conditions including macular degeneration, which affects about 500,000 mainly elderly people in Britain, was many years away.

Professor Ali, the head of the division of molecular therapy at UCL's Institute of Ophthalmology said: "If we can establish the technique of delivering genes to the retina, it paves the way for applying it to other inherited disorders for which there is currently no treatment. Then in the longer term that could open the way to the treatment of common conditions such as macular degeneration, for which there are treatments but which aren't particularly good.

"The advantage of using gene therapy over drugs is that you can give it as a single treatment to the back of the eye, avoiding the need for repeated use of drugs. We anticipate the gene transfer is life long."

Robert Johnson, 23, one of the 12 patients in the trial, was born with an inherited disorder called Leber's congenital amaurosis, which has caused his sight to deteriorate progressively.

Mr Johsnon is able to see outlines of objects in daylight but very little after dark and he has been told that his sight will worsen as he ages.

On the day of his operation a few weeks ago, he told the BBC his mood was swinging from "extreme nervousness" to "a bit of excitement". It will be months before he experiences any benefits from the treatment and only then will the researchers be able to declare it a success.

Mr Johnson's disorder is caused by a fault in a single gene called RPE65. The operation involved injecting normal versions of the defective gene into the pigment cells at the back of the eye. The gene is carried by a virus - modified to render it harmless - which inserts it into the cells' DNA.

The procedure had never been attempted before and was the riskiest part of the treatment, requiring extreme surgical precision. In order to deliver the gene to as many cells as possible, a large volume of solution was injected sufficient to lift the retina causing a temporary detachment. The retina is delicate and one slip could have torn it, destroying Mr Johnson's remaining sight. Mr Johnson was monitored to ensure his retina reattached within 24 hours.

James Bainbridge, a consultant ophthalmologist at Moorfields who carried out the operation on Mr Johnson, said he was pleased with the outcome of the surgery but there was no guarantee it would be a success. "It is very encouraging that we can deliver genes to an extremely fragile site in the eye without complications. But we don't know for sure how someone like Robert's retina will behave in this situation," said Dr Bainbridge. The research team has been experimenting with gene therapy for 15 years but this is the first trial in humans. Dogs affected by the disorder who were treated with the technique had their vision improved to the point where they could walk through a maze without difficulty, which they had previously been unable to do.

As inherited retinal degeneration is a progressive disorder, the best results are likely to be seen in the youngest patients, whose sight has deteriorated least. Professor Tony Moore, a retinal specialist at UCL and part of the research team, said: "Some indications of the results of the trial may be available within several months. It will be many months before we have the full picture."

The announcement of the trial was welcomed by specialists in genetics. Professor Leonard Seymour, the president of the British Society for Gene Therapy, said: "The retina is a really good place for gene therapy because it can be accessed by direct injection - overcoming the problem of gene delivery. When gene delivery is efficient, the whole power of gene therapy is unleashed. The diseased cells in the retina are well documented - there is a good chance of success here."

The research is supported with £1m from the Department of Health. Lord Hunt, the Health minister, said yesterday: "The UK leads Europe in gene therapy with over 40 per cent of clinical trials, second only to the US."