Inherited Blindness Treated With Gene Therapy

Using a revolutionary new gene therapy, scientists in the UK have successfully treated a teenage patient who has a rare inherited blindness called Leber's congenital amaurosis (LCA). The results could have a significant effect on the treatment of eye disease said the researchers.

The world's first landmark clinical trial to test the new gene therapy is the work of researchers from the Institute of Ophthalmology at University College London (UCL) and Moorfields Eye Hospital NIHR Biomedical Research Centre, London, and is published in the early online issue of the New England Journal of Medicine (NEJM), on 27th April. The article includes video footage.

The trial began in February 2007 and involved young patients with LCA, a rare, inherited disease of the retina that appears either at birth or shortly after and progressively leads to loss of vision. It is caused by a faulty gene known as RPE65 which stops the light sensitive cells in the retina (photoreceptors) from working properly.

The project had two goals. First to test whether gene therapy would be safe for patients with retinal disease, and secondly to test whether it could improve vision in young adults with an advanced retinal disease.

The trial was led by Robin Ali Professor of Human Molecular Genetics at UCL Institute of Ophthalmology and Head of the Division of Molecular Therapy. He was accompanied by eye surgeon, James Bainbridge, a Wellcome Trust Advanced Fellow at UCL Institute of Ophthalmology and Consultant Ophthalmologist at Moorfields Eye Hospital, and retinal specialist, Tony Moore, who is Professor of Ophthalmology at UCL Institute of Ophthalmology and Consultant Ophthalmologist at Moorfields Eye Hospital and Great Ormond Street Hospital for Children.

Ali said:

"Showing for the first time that gene therapy can work in patients with eye disease is a very significant milestone."

"This trial establishes proof of principle of gene therapy for inherited retinal disease and paves the way for the development of gene therapy approaches for a broad range of eye disorders," he added.

In the trial, Ali and colleagues inserted healthy copies of the faulty RPE65 into the cells of the retina of three young adults using a harmless virus or "vector" to carry the gene. The vector was engineered by the US company Targeted Genetics.

Baimbridge explained what they did:

"We developed surgical techniques to enable access to the cells beneath the retinas of patients, using a very fine needle to deliver the modified virus in a controlled retinal detachment that resolves as the vector is absorbed."

All three patients achieved levels of vision that was at least the same as before the operation, but one patient in particular, 18-year old Steven Howarth, showed significantly improved night vision. Tests before and after the operation showed that Howarth's ability to negotiate an "obstacle course" simulation of a night-time street significantly improved in that he carried out tasks faster and with fewer mistakes after the operation.

But perhaps the most crucial result of the trial was that it was found to be safe. There were no side effects.

Baimbridge said they were all very excited that the method can "improve vision in a condition previously considered wholly untreatable", and that the method was safe, especially since retinal tissue is very fragile.

Speculating on why only Howarth's vision improved after the therapy, the researchers said perhaps it was because his LCA was not as advanced as it was in the other two patients. It is possible that the other two patients may still show improvement in the future, they said, but it could be a while before they notice.

Moore said:

"It is very encouraging to see that this treatment can work, even in young adults who have severely advanced disease."

"We anticipate an even better outcome in the younger patients we are now beginning to involve as the trial proceeds, as we will be treating the disease in the early stages of its development," he added.

Ali cautioned that while they were all very excited about the improvement in Howarth's vision:

"It's important to emphasize that gene therapy is still an experimental treatment not yet generally available to patients."

He said they will be testing the method with other LCA patients, and with patients who have other types of retinal disease.

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