Gene therapy for rare eye condition

A gene therapy for a rare form of blindness has brought “hope to millions affected by eye diseases”, reported The Independent today. The story of a teenager who experienced a life-changing improvement in his vision after being treated with a gene therapy was covered by most of the national newspapers.

The study behind these stories is a small one that was primarily assessing whether gene therapy was a safe way to treat this particular inherited eye disorder – Leber’s congenital amaurosis. The treatment was found to be safe, though it only seemed to have a significant effect in one of the three patients it was used in.

The findings are of relevance to the scientific and medical community and represent an important step forward in treatments for congenital disorders (those present at the time of birth). It’s important to note that at present the technology is only relevant for this one rare eye disorder – not all types of ‘blindness’.

As this therapy is at an early stage of development, more research in a larger group of people is needed. This is already underway in a group of children with the condition.

Where did the story come from?

Dr James Bainbridge and colleagues from the Institute of Ophthalmology at University College London; Moorfields Eye Hospital in London, and the Michigan State University and Targeted Genetic Corporation, Seattle in the US. The study was funded by the UK Department of Health, the British Retinitis Pigmentosa Society and the Special Trustees of Moorfields Eye Hospital.

The study was published in the peer-reviewed medical journal: the New England Journal of Medicine .

What kind of scientific study was this?

In this case series, three patients with severe retinal dystrophy were given an experimental gene therapy for their condition. This eye disorder results from a mutation in a gene that codes for a protein in the pigmented cells of the retina (the RPE65 gene). The product of this gene – the 65-kD protein is a vital part of the vision cycle and without it, vision is affected. The condition – part of a family of inherited eye disorders called Leber’s congenital amaurosis - is associated with poor vision at birth and can lead to complete loss of vision in early adulthood.

The researchers were testing out a new gene therapy that targets the defective gene in the eye with a harmless virus containing a healthy copy of the gene. Viruses are often used in gene therapies to carry genes to particular sites. As they use human DNA to multiply, they are good ‘vectors’ (carriers) for this technology.

Previous research had found this particular gene therapy to be effective for the condition in dogs, and the researchers were interested in whether the treatment would also work in humans with the condition. The main aim of the study was to see whether it was a safe therapy and secondly what effects it would have on sight.

The three participants were aged between 17 and 23 and all of them had early onset retinal dystrophy caused by RPE65 mutations. From an early age, all the patients had experienced little or no vision in low light conditions, but had limited vision when the light was good.

The participants had surgery where the virus transporting the genes was delivered in a liquid solution to the retina. A course of steroids to prevent inflammation was given to them and their vision was tested regularly after the treatment (at two, four, six, and 12 months).

The researchers were mainly looking at whether there were any serious adverse effects of the treatment, but they were also assessing whether the sight of the patients improved.

What were the results of the study?

There were limited adverse effects of the procedure. Some mild inflammation was expected and this was managed with steroids. There was no evidence that the virus had disseminated (i.e. moved outside of the retina). As the therapy had been delivered beneath the retina, this resulted in some temporary retinal detachment and reduction in clarity of vision. After six months, this had returned to preoperative levels in all patients.

There was no clinically significant improvement in any of the patients visual acuity (clarity of vision) or in their peripheral vision. The only significant improvement found was in patient three, whose vision in low light/darkness improved.

What interpretations did the researchers draw from these results?

The researchers conclude that there are no immediate adverse effects from the treatment, and that this type of gene therapy can lead to modest improvements in visual function, even in people with advanced degeneration.

They say that children are more likely to benefit from this treatment than adults and that their findings provide support for the development of further clinical studies in children with the RPE65 mutation that leads to vision problems.

What does the NHS Knowledge Service make of this study?

The main aim of this study was to determine whether the treatment was safe for use in humans and that it did not have any major side effects. In this regard, it was successful as it found the gene therapy to be safe. Jumping this major hurdle paves the way for future studies.

It should be pointed out that, at present, the treatment is only applicable to the eye condition that this study focussed on - an inheritable disorder of particular cells in the retina. It will not be useful for sufferers of many other vision disorders that can lead to blindness. However, the methods used here to deliver the carrier virus to the retina could be an option for other conditions.

The technology is groundbreaking and the success of the treatment (even if it is only in one of three patients) is important. Further work is currently underway in a larger group of children with the condition.