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

Cideciyan, Artur V; Jacobson, Samuel G; Ho, Allen C; Garafalo, Alexandra V; Roman, Alejandro J; Sumaroka, Alexander; Krishnan, Arun K; Swider, Malgorzata et al. · Nat Med · 2021

case_report · Level V

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Abstract

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 foveal cone photoreceptors.

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