Promising first results in gene therapy trial for inherited blindness

Promising results from the first clinical trial of a gene therapy for an inherited cause of progressive blindness called choroideremia are published today in the 'Lancet'. The phase I clinical trial is funded by the Health Innovation Challenge Fund, a partnership between the Wellcome Trust and the Department of Health.

The aim of the treatment in this study was to get the gene therapy into the cells in the retina of the eye without causing damage. After six months, however, the patients actually showed improvements in their vision in dim light and two of the six were able to read more lines on the eye chart.

A total of nine patients have now had one eye treated with the gene therapy in operations at the Oxford Eye Hospital, part of the Oxford University Hospitals NHS Trust. The therapy is given in one eye to allow comparison with progression of the disease in the other eye.

Results at six months are today reported for the first six patients in the 'Lancet'. The first patient to receive the operation has now been followed up for over two years. Based on the success of the treatment in the first six patients, three more have recently been tested at a higher dose.

Professor Robert MacLaren of the Nuffield Laboratory of Ophthalmology at the University of Oxford, and a consultant surgeon at the Oxford Eye Hospital and honorary consultant at Moorfields Eye Hospital, led the development of the retinal gene therapy and this first clinical trial. He says: "It is still too early to know if the gene therapy treatment will last indefinitely, 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.

"The results showing improvement in vision in the first six patients confirm that the virus can deliver its DNA payload without causing significant damage to the retina. This has huge implications for anyone with a genetic retinal disease such as age-related macular degeneration or retinitis pigmentosa, because it has for the first time shown that gene therapy can be applied safely before the onset of vision loss."

The first patient to be treated, Jonathan Wyatt, 65, says: "My left eye, which had always been the weaker one, was that which was treated as part if this trial... Now when I watch a football match on TV, if I look at the screen with my left eye alone, it is as if someone has switched on the floodlights. The green of the pitch is brighter, and the numbers on the shirts are much clearer."

Choroideremia is a rare inherited cause of blindness that affects around 1 in 50,000 people. The first signs tend to be seen in boys in late childhood, with the disease slowly progressing until vision is lost. There is currently no cure. It is caused by defects in the CHM gene on the X chromosome, which explains why it is almost always males who are affected. Without the protein produced by the CHM gene, pigment cells in the retina slowly stop working, then die off. As the disease progresses, the surviving retina gradually shrinks, reducing vision.

The gene therapy approach developed by Professor MacLaren’s team uses a small, safe virus to carry the missing CHM gene into the light-sensing cells in the retina. In an operation similar to cataract surgery, the patient’s retina is first detached and then the virus is injected underneath using a very fine needle. The aim is for the CHM gene, once delivered into the cells of the retina, to start producing protein and stop the cells dying off.

This is the first time that a gene therapy has targeted the principal light-sensing cells in the retina, known as photoreceptors. This means the approach has relevance for other, far more common causes of blindness in which these light-sensing cells are affected, such as retinitis pigmentosa and age-related macular degeneration.

Wayne Thompson, 43, an IT project manager in Staffordshire, was treated in April with a higher gene therapy dose as part of the subsequent trial: "One night in the summer, my wife called me outside as it was a particularly starry evening. As I looked up, I was amazed that I was able to see a few stars. I hadn’t seen stars for a long, long time... For a long time I lived with the certainty of losing vision. Now I have uncertainty of whether the trial will work, but it is worth the risk."

Dr. Ted Bianco, Director of Technology Transfer at the Wellcome Trust said "Whilst it is important to recognise that it is early days in assessing this new treatment, it is good to see the encouraging results of this trial to find safe and effective approaches to patient care based on gene therapy. Pioneering work like this helps lay down the foundations for a wide array of potential, future treatments of people living with genetic disorders."

The research has received additional support from the National Institute for Health Research Oxford Biomedical Research Centre and the charity Fight for Sight, the main UK charity that funds pioneering eye research to prevent sight loss and treat eye disease.