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

Nat Med. 2021 May;27(5):785-789. doi: 10.1038/s41591-021-01297-7. Epub 2021 Apr 1.


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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Ciliopathies / genetics
  • Ciliopathies / therapy*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Genetic Therapy / methods*
  • Humans
  • Leber Congenital Amaurosis / genetics
  • Leber Congenital Amaurosis / physiopathology
  • Leber Congenital Amaurosis / therapy*
  • Oligonucleotides, Antisense / therapeutic use*
  • Photoreceptor Cells / metabolism
  • Vision, Ocular / physiology
  • Visual Fields / physiology


  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Oligonucleotides, Antisense

Associated data

  • ClinicalTrials.gov/NCT03140969