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Gene therapy for Leber congenital amaurosis (LCA) caused by damage to the RPE65 geneUCL Institute of Ophthalmology Department of GeneticsWe conducted the worlds first clinical trial assessing the safety and efficacy of viral gene therapy for inherited sight loss (Bainbridge et al 2008)Leber congenital amaurosis and the RPE65 geneLCA is a severe inherited retinal disease in which vision is affected from birth and continues to worsen in early adulthood, leading to complete blindnessRPE65 is one of many genes associated with LCADamage to the RPE65 gene means that retinal pigment epithelium (RPE) cells underlying the light-sensitive photoreceptor cells cannot recycle the visual pigment used to detect lightWhy was LCA caused by damage to RPE65 the first eye gene therapy trial?The genetic cause of the disease is well understoodAlthough vision is affected early in life and worsens over time, photoreceptor cells remain healthy in the early stages of disease so they can be targeted by gene therapy vectorsWe have established proof-of-principle that RPE65 gene replacement restores vision in small and large animal modelsThe intervention might improve visual function rather than just slow sight lossRPE65 clinical trial surgical procedureKey hole surgery is used to pass a fine probe into the vitreous jelly at the back of the eyeThe virus suspension is then injected underneath the retina, causing a temporary elevation of the retina this detachment usually disappears the following dayRecovery from gene therapy surgery is similar to other types of retinal surgery, and patients can normally return to normal activities within 2 weeks

Improvements in vision following gene therapySeveral patients have shown improvements in visual function with a variety of testsPatients have shown improved peripheral vision when tested under dim lighting conditions (shown by the green bars)

Improvements in vision following gene therapyPatients have shown improvements in their central vision when tested with light stimuli to the central retina (shown by the white circles below)

Improvements in vision following gene therapySome patients have also shown improvements in their ability to navigate through an obstacle course in dark conditions, showing that improvements can be useful in day to day navigation

Improved night vision following gene therapyConclusions and future plansRetinal gene therapy is safe to perform in the eyeResults so far suggest that it can improve visual functionThe success of this trial for LCA paves the way for gene therapy trials for many other types of retinal diseases