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.
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
Substances
-
Antigens, Neoplasm
-
Cell Cycle Proteins
-
Cep290 protein, human
-
Cytoskeletal Proteins
-
Oligonucleotides, Antisense
Associated data
-
ClinicalTrials.gov/NCT03140969