Eyeworld

EW NEWS & OPINION 36 September 2015 by Maxine Lipner EyeWorld Senior Contributing Writer tained in some participants for up to 3 years." However, the peak levels of improvement have declined in that time. Investigators found that these tended to peak 6–12 months after treatment, modestly improving visual sensitivity for a short period. Investigators are now working on ways to prolong the effect. While repeating the process is one pos- sibility, investigators believe there may be a better way, Dr. Bainbridge said. "Because the injection carries some risk, it would be preferable to improve on the durability of a single injection rather than to perform multiple injections," he said, adding that it would be safer to have a more sustained effect after a single injection than to subject the patient to multiple injections. "We have designed and manufactured a new vector that is designed to be more powerful, more potent, and more long-lasting." Broader implications Dr. Bainbridge thinks the approach will have a broader impact aside from Leber congenital amaurosis. "We anticipate that this approach is likely to benefit people with inherit- ed retinal diseases when the inter- vention can be made available to them at a relatively early stage of the condition, before there is established degeneration," he said, adding that the gene therapy approach can't be expected to reverse retinal degen- eration. With the Leber congenital amaurosis patients he expects that the earlier the treatment can be given, the better. Dr. Bainbridge hopes that prac- titioners come away from the recent study with the realization that gene therapy has solid potential. "The take-home message is that gene therapy can improve sight in people with inherited eye disease," he said. "But for a sustained preservation of sight we need to look to develop more powerful, more potent vector systems." EW Editors' note: Dr. Bainbridge has financial interests with Athena Vision (London). Contact information Bainbridge: j.bainbridge@ucl.ac.uk the genes are carried by a viral vec- tor. Such vectors consist of viruses that have been disabled in order to carry the normal gene into the cells that are targeted. "It's disabled so it can't cause the spread of infection," Dr. Bainbridge said. Once the gene is available in the cell, it provides information to generate the RPE65 protein and restore normal recycling of the visual pigment that otherwise would be suspended. The study included 12 children and young adults affected by Leber congenital amaurosis as a result of defects in the gene RPE65. "The oldest was 23 years and the youngest was 6 years of age," Dr. Bainbridge said. While this was the first time the therapy was performed in humans, subsequent studies performed by other groups have looked at similar therapy. "All trials have demonstrat- ed some improvement in aspects of sight," Dr. Bainbridge said. Results from his study have been promis- ing. "Findings have shown that the gene therapy resulted in improve- ment in night vision in many of the participants," he said. "These improvements have been main- childhood," Dr. Bainbridge said. "Then they lose daylight vision progressively during the first decade of life." Initiating gene therapy This condition can be caused by a mutation in the gene responsible for encoding the protein RPE65, he explained, adding that this gene is critical for recycling of visual pigment and so is crucial for normal sight. "We have been finding out if by providing a normal copy of the gene that they lack, we can improve their night vision and protect their daylight vision," he said. Since this disease is caused by a lack of the normal gene, the idea is to replace that defective gene with a regular one. "In principle the gene therapy is simple because the aim is to compensate for that deficien- cy by providing a normal working copy of the gene to the cells in the eye that need it," Dr. Bainbridge explained. "But the cells that need it are underneath the retina." In order to deliver the genes to those cells, investigators inject them during a surgical procedure underneath the retina in a suspension form in which Considering first in human trial results F or patients with Leber con- genital amaurosis, the visual prognosis has always been grim. But gene therapy is offering new hope, accord- ing to James Bainbridge, MD, Uni- versity College London Institute of Ophthalmology and Moorfields Eye Hospital, London. Dr. Bainbridge and fellow investigators recently re- ported on results involving the first gene therapy trial in humans, which appeared in the May 2015 issue of the New England Journal of Medicine. While Leber congenital amau- rosis is an unusual condition, it's one of the most common causes of sight loss that affects infants. "It causes severe damage to sight at a very young age and that's why it's so important," he said. "It becomes apparent within the first year or two of life that [the child has] severe impairment of sight." Children born with this genet- ic condition have very poor night vision from the start. "They have a lack of night vision, but they can retain some daylight vision in early Gene therapy inroads for Leber congenital amaurosis

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