Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect

Nat Med. 2019 Feb;25(2):225-228. doi: 10.1038/s41591-018-0295-0. Epub 2018 Dec 17.

Abstract

Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3 months. The visual acuity of one exceptional responder improved from light perception to 20/400.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antigens, Neoplasm / genetics
  • Cell Cycle Proteins
  • Cilia / drug effects
  • Cilia / pathology*
  • Cytoskeletal Proteins
  • Female
  • Humans
  • Intravitreal Injections
  • Leber Congenital Amaurosis / drug therapy*
  • Leber Congenital Amaurosis / physiopathology*
  • Male
  • Neoplasm Proteins / genetics
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / therapeutic use*
  • Photoreceptor Cells, Vertebrate / pathology*
  • Vision, Ocular*
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT03140969