Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report

Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with the antisense oligonucleotide (AON) sepofarsen. One patient who was part of a larger cohort (ClinicalTrials.gov NCT03140969) was studied for 15 months after a single intravitreal sepofarsen injection. Concordant measures of visual function and retinal structure reached a substantial efficacy peak near 3 months after injection. At 15 months, there was sustained efficacy, even though there was evidence of reduction from peak response. Efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and a slow natural rate of CEP290 protein degradation in human fovea! cone photoreceptors.

Automated summary

Treatment of Leber congenital amaurosis due to CEP290 ciliopathy using antisense oligonucleotide (AON) sepofarsen shows significant efficacy, with sustained efficacy observed at 15 months despite a reduction from peak response. The efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and the slow natural rate of CEP290 protein degradation in human fovea cone photoreceptors.