Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report.
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ABSTRACT:
SUBMITTER: Cideciyan AV
PROVIDER: S-EPMC8127404 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report.
Cideciyan Artur V AV Jacobson Samuel G SG Ho Allen C AC Garafalo Alexandra V AV Roman Alejandro J AJ Sumaroka Alexander A Krishnan Arun K AK Swider Malgorzata M Schwartz Michael R MR Girach Aniz A
Nature medicine 20210401 5
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 redu ...[more]
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Project description:PurposeAn intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A > G variant in the CEP290 gene. A previous report showed vision improvements following a single injection in one eye with unexpected durability lasting at least 15 months. The current study evaluated durability of efficacy beyond 15 months in the previously treated left eye. In addition, peak efficacy and durability were evaluated in the treatment-naive right eye, and re-injection of the left eye 4 years after the first injection.ObservationsVisual function was evaluated with best corrected standard and low-luminance visual acuities, microperimetry, dark-adapted chromatic perimetry, and full-field sensitivity testing. Retinal structure was evaluated with OCT imaging. At the fovea, all visual function measures and IS/OS intensity of the OCT showed transient improvements peaking at 3-6 months, remaining better than baseline at ∼2 years, and returning to baseline by 3-4 years after each single injection.Conclusions and importanceThese results suggest that sepofarsen reinjection intervals may need to be longer than 2 years.
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