Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy
Authors
Pennesi, Mark E.Weleber, Richard G.
Yang, Paul
Whitebirch, Chris
Thean, Beverly
Flotte, Terence R.
Humphries, Margaret
Chegarnov, Elvira
Beasley, Kathleen N.
Stout, J. Timothy
Chulay, Jeffrey D.
Document Type
Journal ArticlePublication Date
2018-07-24Keywords
AAVLeber congenital amaurosis
RPE65
gene therapy
retinal degeneration
Enzymes and Coenzymes
Eye Diseases
Genetic Phenomena
Genetics and Genomics
Pediatrics
Therapeutics
Metadata
Show full item recordAbstract
Previously, results at 2 years after subretinal injection of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in eight adults and four children with retinal degeneration caused by RPE65 mutations were reported. Now, results at 5 years after treatment in 11 of these subjects are reported. Subjects received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of two dose levels, and were followed for 5 years after treatment. The primary safety outcomes were ocular and non-ocular adverse events. Efficacy outcomes included changes in best corrected visual acuity, static perimetry hill of vision measurements for the central 30 degrees (V30), and total (VTOT) visual field and kinetic perimetry visual field area. The only adverse events reported during years 3, 4, and 5 were minor intercurrent illnesses. Pediatric subjects had improvement in visual acuity and static perimetry in the treated eye, sometimes with a smaller improvement in the untreated eye, during the first 2 years of the study that persisted during years 3-5, with no consistent changes in kinetic perimetry during the study. Most adult subjects had no consistent changes in visual acuity or static perimetry during the study. Three adult subjects with markedly abnormal baseline kinetic visual field area had improvement in the treated eye during the first 1-2 years after treatment, but the absolute magnitude of the improvement was small and was not sustained at subsequent visits. There were no clinically significant adverse events. Visual acuity and static perimetry testing results suggest that treating patients at a younger age is associated with better visual function outcomes during 5 years after treatment.Source
Hum Gene Ther. 2018 Jul 24. doi: 10.1089/hum.2018.014. [Epub ahead of print] Link to article on publisher's site
DOI
10.1089/hum.2018.014Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43652PubMed ID
29869534Related Resources
ae974a485f413a2113503eed53cd6c53
10.1089/hum.2018.014