Essay Example on Vector administration The extension of the bleb of subretinal Vector

There was a progressive improvement in the retinal sensitivity for up to four hours in dark adaptation Participants 3 5 6 8 and 10 reported advancements in night vision whereas participants 5 8 and 10 showed refinements in the navigation of vision guided ambulatory Participant 4 was the only subject who subjectively reported an improved night vision with no consistent measurement in retinal navigation and sensitivity Spectral sensitivity Participants 5 and 6 were confirmed to have substantial improvements in the measurement of spectral sensitivities in the superior retina at a fixed location following the administration of the higher dose This was 10 to 100 times as high in rod sensitivity that had a peak 12 months after treatment before declining subsequently Participant 6 had greater improvements that indicated recovery of rod function Participant 5 also had similar improvements of 500 nm and 600 nm that showed cone function improvement Visual acuity Participant 11 had an improvement in visual acuity with a similar improvement in the untreated contralateral eye Participants 3 and 7 experienced visual acuity decline by more than 15 letters on the ETDRS chart Participant 12 had a modest acuity but with a sustained decline in the study eye The decline in participants 7 and 12 was associated with a subjective deterioration of vision ERG The use of ERG at baseline were undetectable as measured by the rod photoreceptor mediated responses None of the participants had a significantly sustained rod in cone or rod responses Participants who retained the same function level has very low amplitude residual ERD findings Inflammatory and immune responses 

No magnitude improvement could be detected by means of ERG On the contrary there was a robust RPE65 deficiency in the responses after the same intervention in animal models Our results provided further evidence for the improved function of the rod photoreceptor in response to the AAV2 mediated RPE65 gene supplementation Substantial improvements in the retinal function in dogs were measurable by means of ERG Although they could offer protection against degeneration they were highly dose dependent The improvements in retinal sensitivity in humans were modest even in participants who had mild retinal degeneration and never had the protection against ongoing degeneration Therefore we can make the decision that gene therapy with a rAAV2 2 vector that carries RPE65 cDNA led to a temporary and incomplete restoration of retinal function in humans This partially reflects an unmet demand for RPE65 that is persistent Conclusions Retinal sensitivity was improved by the gene therapy rAAV2 2 RPE65 vector There is a species difference in the required amount of RPE65 that is required to drive the visual cycle in comparison with the obtained result in the dog model The RPE65 demand for affected persons wasn't met to the required extent for a durable and robust effect