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Gene therapy treatment for rare eye disease choroideremia has been shown to not only stall degeneration, but improve the sight of patients involved in the first UK trial.

The BBC reported the news today, having first reported the launch of the trial back in October 2011. The story follows the progress of one particular volunteer, an arbitration lawyer named Jonathan Wyatt who at the start of the trial was aged 63 and beginning to struggle to work because of the degeneration. Now, he can read three lines further down the optician's chart. "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," a roundup of the news on the University of Oxford website reveals. "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."


Choroideremia is a rare genetic disorder, affecting around one in every 50,000 to 100,000 people, mainly men. However the prognosis is definitive -- what begins as a struggle to see in the dark in childhood or the teenage years, progresses on to tunnel vision and will ultimately result in total blindness. It is the result of photoreceptor cells -- light-sensitive cells round the retina -- gradually dying off. The disease is caused by a mutation in the CHM gene, which controls the production of the REP-1 protein. This protein is responsible for the activity of another protein, known as Rab, which controls the movement of proteins within cells. When the CHM gene is faulty, REP-1 is not produced and there's nothing to promote cell activity. This effects the choroids, blood vessels located between the retina and the sclera that provide the retinal pigment epithelium and photoreceptors with oxygen. Both the choroids and the retinal pigment epithelium are responsible for thriving photoreceptors, which in turn convert light into electrical impulses our brain translates into images. As the disease progresses, the retina will shrink, thus demising the field of vision.

In 2011, professor Robert MacLaren of the Nuffield Laboratory of Ophthalmology at University of Oxford, working in conjunction with Moorfields Eye Hospital, launched a trial to test the reintroduction of the REP-1 gene in the eye. The 24-month trial involved 12 people, all of whom had the REP-1 gene injected straight to the photoreceptors in the retina using a manmade virus.

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Two different doses were trialled, and it seems that Wyatt's recovery was the result of the stronger dose -- in fact, because of the success to date of the trial, three additional patients are now set to receive the higher dose. "My left eye, which had always been the weaker one, was that which was treated as part of this trial," said Wyatt in a statement. "Now when I watch a football match on the 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."

Another candidate, 43-year-old Wayne Thompson, received the stronger dose and found he could see stars again for the first time in many years. "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."

The results of the first six months of the trial involving six of the patients has been published in the Lancet, where a synopsis of the results breaks down the progress: "Despite undergoing retinal detachment, which normally reduces vision, two patients with advanced choroideremia who had low baseline best corrected visual acuity gained 21 letters and 11 letters (more than two and four lines of vision). Four other patients with near normal best corrected visual acuity at baseline recovered to within one to three letters. Mean gain in visual acuity overall was 3·8 letters."

MacLaren is hopeful that this trial, albeit in its early stages and concerning a small group with a very specific disorder, could pave the way for gene therapy targeting all manner of degenerative eye disorders and blindness. "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," he said. "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 synopsis in the Lancet adds that if any gene therapy treatment were to be trialled for age-related macular degeneration, it should take place before the onset of retinal thinning. This is why it's vital small, specific trials like this one by MacLaren take place first. There is always a risk that introducing the virus and gene at the early stages of a disorder could have a negative effect on the healthy remaining retina. This has to be ruled out before trials can take place at the earlier stages of the disease.

Currently, options open to sufferers of other, more common degenerative eye diseases, are few. Some have been able to trial the Argus II, a bionic eye being trialled in Europe. It is suitable for those with the genetic disorder retinitis pigmentosa, where the eye's rods and cones again stop functioning properly. The implant generates the electrical signals where the remaining cells no longer can, but it's a basic interpretation so the brain will process these signals as flashes of light and things of that nature. It also relies on an external component, a small camera mounted on a pair of glasses, which captures whatever the individual is looking at, sends this to a computer which transforms it into a pixelated image that is in turn transferred wirelessly to the implant in the eye. Electrodes attached to the implant stimulate the optical nerve in the same pattern as the pixelated image.

MacLaren's study was funded by the UK Department of Health and the Wellcome Trust, with added help from the National Institute for Health Research Oxford Biomedical Research Centre and charity Fight for Sight.