Eye gene therapy breakthough: the significance

A team based at the UCL Institute of Ophthalmology/Moorfields has announced exciting results for gene therapy in the eye.

Professor Adrian Thrasher at the UCL Institute of Child Health led the team which announced the UK's first gene therapy clinical success.   Professor Thrasher, who was also an author on the Institute of Ophthalmology/ Moorfields study, said
"These are highly significant findings. Previous clinical success for gene therapy has been confined to genetic modification of bone marrow stem cells in patients with diseases of the immune system as we have shown at GOSH. We've worked very closely together on both these projects for many years now, so its exciting and rewarding to see benefits in patients with inherited form of blindness as well. More importantly, it offers a view of how genetic medicines can offer realistic treatments for a whole range of genetic disorders, and we are working hard at doing this."

UCL Institute of Child Health and Great Ormond Street Hospital for Children is the world’s leading centre for successful gene therapy in children.  We have reported clinical successes for two inherited immune diseases, X-SCID, where ten patients have been treated, and ada-SCID, where five patients have been treated.  All X-SCID children and some ada-SCID children have seen significant clinical benefit.   A new X-SCID trial will be launched later in the year with an improved vector, and by December 2008 we expect to be in clinical trials for four life threatening inherited immune diseases.

UCL Press Release

Results of world’s first gene therapy for inherited blindness show sight improvement

UK researchers from the UCL Institute of Ophthalmology and Moorfields Eye Hospital NIHR Biomedical Research Centre have announced results from the world’s first clinical trial to test a revolutionary gene therapy treatment for a type of inherited blindness. The results, published today in the New England Journal of Medicine, show that the experimental treatment is safe and can improve sight. The findings are a landmark for gene therapy technology and could have a significant impact on future treatments for eye disease.

The trial, conducted in the NIHR Biomedical Research Centre which received additional funding from the Department of Health, represented a world first when it began in February 2007. It involves young patients with a condition called Leber’s congenital amaurosis (LCA), a rare inherited eye disease caused by an abnormality in a gene called RPE65. The condition appears at birth or in the first few months of life and causes progressive deterioration and loss of vision. There are currently no effective treatments available. The trial’s purpose was firstly to find out whether gene therapy for retinal disease is safe, and secondly to find out if it can benefit vision in young adults who already have advanced retinal disease.

Crucially, the experimental treatment was found to cause no side effects in this trial. Following the treatment, the three patients involved underwent a series of tests designed to establish the effects of the therapy on vision. They all achieved levels of vision at least equivalent to before the operation, but one patient (Steven Howarth, 18) benefited from significantly improved night vision. This was demonstrated by his ability to negotiate a specially constructed simulation of a night-time street scene. Before the operation he completed the task slowly and made several mistakes, but following the surgery he was able to navigate quickly and without mistakes. (Video available for media release – please see Notes to Editors.)

The researchers believe the operation’s success for this particular patient could be because his disease had not progressed to the same extent as the others. The other two patients may also still benefit from the new treatment in the future, but it will be some time before this becomes apparent. The team have already begun to trial the technique in younger patients, where they hope to achieve even better results.

The team conducting the trial is led by Professor Robin Ali and includes eye surgeon Mr James Bainbridge and retinal specialist Professor Tony Moore. The technique used in the trial involved inserting healthy copies of the missing RPE65 gene into the cells of the retina to help them to function normally. This involved an operation which delivered the normal genes to the retina, using a harmless virus or ‘vector’ to carry the gene into the cells – the vector was manufactured by US company Targeted Genetics.

Commenting on the findings, Professor 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.”

Explaining the technique, Mr James Bainbridge, who leads the surgical team, said: "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. It is tremendously exciting to see that this technique is safe in an extremely fragile tissue and can improve vision in a condition previously considered wholly untreatable."

Professor 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.”

Professor Ali added: “These results give us great confidence that this technique is safe and can bring real benefit to patients with impaired vision. While we’re very excited about the improvement in Steven’s vision, it’s important to emphasise that gene therapy is still an experimental treatment not yet generally available to patients. The technique will be tested in other patients with LCA and we also hope to begin trials for other forms of retinal disease in the future.”