Patient information for gene therapy

Clinical trial of gene therapy for LCA

Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology

Information for patients

Background

This trial, which received funding from the Department of Health, was a world first when it began in 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 in vision. There are currently no effective treatments available.

The first results of the trial, which were published on 27th April in the New England Journal of Medicine, show that gene therapy can be 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 technique used in the trial involved inserting healthy copies of the 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 trial’s purpose is 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.

In February 2007, 23-year old Robert Johnson was the first patient included in the trial, becoming the first person to undergo gene therapy for an inherited eye disorder. Subsequently, two other young adults were included. Crucially, the experimental treatment has caused no side effects in this trial. Following the treatment, the patients took part in 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, 18yr old Steven Howarth, 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. Following treatment Steven was able see targets projected onto his retina and points of light when previously he had been unable to. Crucially he was also able to easily negotiate a maze designed to test his ability to see in dimly lit and dark environments.

Gene therapy is likely to be most effective in younger patients in whom the retina, whilst poorly functioning, remains structurally intact. In the first stage of our trial we chose patients with safety in mind. However, in the case of Steven Howarth evidence of improved vision was found despite advanced disease. We believe the operation’s success in this particular patient could be because his disease had not progressed to the same extent as the others. The other patients may also still benefit from the new treatment in the future, but it will be some time before this becomes apparent. We have already begun to trial the technique in younger patients, where we hope to achieve even better results.

The successful use of gene therapy to treat early-onset retinal dystrophy in patients is the culmination of 15 years work by scientists and ophthalmologists at UCL Institute of Ophthalmology and Moorfields Eye Hospital, and builds on the work of other groups based in Europe and the United States.

This study constitutes a landmark in the treatment of genetic disorders which result in blindness. As the trial continues and children with less advanced disease are included it is hoped that treatment will be demonstrated to restore vision to normal levels and allow patients to lead even more active lives.

These results give us great confidence that this technique is safe and can bring real benefit to patients with impaired vision. While these results are enormously encouraging, it is 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 near future. Patients with genetic mutations responsible for other forms of retinal dystrophy can be encouraged by results of this trial, but extensive further work will be needed before they can benefit from the technology.
 
Since the effect of gene therapy depends on the presence of surviving cells, it is not expected to help in conditions where there is very significant retinal damage. In these conditions, cell transplantation techniques and stem cell approaches offer a great deal of promise. Work in this field is progressing in our laboratory and in many others internationally.

Frequently asked questions

What is retinal dystrophy?

Retinal dystrophy is a term for a large number of retinal diseases (or degenerations), frequently inherited, which cause similar symptoms and retinal appearances in affected patients.

A number of defective genes cause ‘retinal dystrophy’ which is collectively the commonest cause of blindness in young people in the developed world. Patients with the ‘RPE65’ form of retinal dystrophy have difficulty in negotiating dark or dimly lit environments.

How can I get involved in this trial?

Our current trial involves people whose condition is caused specifically by defects in the RPE65 gene. If you know that you have a mutation in RPE65 then you should seek referral to Prof Tony Moore at Moorfields Eye Hospital. Professor Moore and his team will be able to assess your suitability for inclusion in current or future trials.

What if I have a form of retinal dystrophy not caused by the RPE65 mutation?

If you have been diagnosed with a retinal dystrophy and are not aware of the gene responsible we would encourage you to consult your ophthalmologist or seek advice via your GP. Those with mutations in genes other than RPE65 are not suitable for inclusion in the current trial but may benefit from future work. http://www.brps.org.uk/

Your doctor may wish to refer you to Professor Tony Moore at Moorfields Eye Hospital if your mutation is unknown or if you wish to be included on our database containing details of patients and their specific mutations – this valuable resource enables greater understanding of the effects of each mutation and allows us to approach patients directly when opportunities arise.

 Am I too old to take part in the trial?

 Currently we are recruiting children only to the trial because we expect that children are most likely to benefit from treatment.

 Future work will address the extent to which adults can expect to benefit from gene therapy. Work in our lab and other laboratories will also develop alternative treatments including cell transplantation and electronic retinal implants.

I have been diagnosed with age-related macular degeneration – might I benefit from gene therapy?

While it might be possible in the future to treat this condition using gene therapy we are not performing clinical trials for this condition at present.

Work in our laboratory and other is aimed at developing this and alternative treatments such as cell transplantation.

http://www.maculardisease.org/

I have Leber’s optic atrophy. Might I also benefit?

 Leber’s optic atrophy is a condition of the optic nerve and is very different to Leber’s congenital amaurosis. We have no trials ongoing to develop gene therapy for this condition at present but this might be a possibility in the future.

I suffer from glaucoma. Might I benefit?

We have no trials ongoing to develop gene therapy for glaucoma at present but this might be a possibility in the future

http://www.glaucoma-association.com/

I lost vision in my eye as a result of an injury or retinal detachment - might gene therapy restore my vision?

We have no trials to develop gene therapy for eye injuries or retinal detachment at present although this might be a possibility in the future.

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