Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence

Jie Gao,1 Rehan M Hussain,2 Christina Y Weng1 1Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 2Retina Associates, Elmhurst, IL, USACorrespondence: Christina Y WengBaylor College of Medicine, Alkek Eye Center, 1977 Butler Blvd, Houston, TX 77030, USAEmail christina.weng@bc...

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Autores principales:	Gao J, Hussain RM, Weng CY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	gene therapy inherited retinal diseases leber congenital amaurosis luxturna rpe65 voretigene neparvovec retinitis pigmentosa retina Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/6274fcbff62d431f9b72397dcc8d7d15
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spelling	oai:doaj.org-article:6274fcbff62d431f9b72397dcc8d7d152021-12-02T16:03:28ZVoretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence1177-5483https://doaj.org/article/6274fcbff62d431f9b72397dcc8d7d152020-11-01T00:00:00Zhttps://www.dovepress.com/voretigene-neparvovec-in-retinal-diseases-a-review-of-the-current-clin-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Jie Gao,1 Rehan M Hussain,2 Christina Y Weng1 1Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 2Retina Associates, Elmhurst, IL, USACorrespondence: Christina Y WengBaylor College of Medicine, Alkek Eye Center, 1977 Butler Blvd, Houston, TX 77030, USAEmail christina.weng@bcm.eduAbstract: Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed and showed similar diseased phenotypes to their human counterparts. Proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including electroretinograms, pupillary light responses, and object avoidance behaviors. Positive results in animal models led to Phase 1 human studies using adeno-associated viral vectors. Results in these initial human studies also showed positive impact on visual function and acceptable safety. A landmark Phase 3 study was then conducted by Spark Therapeutics using a dose of 1.5 x1011 vector genomes after dose-escalation studies confirmed its efficacy and safety. Multi-luminance mobility testing was used to measure the primary efficacy endpoint due to its excellent reliability in detecting the progression of inherited retinal diseases. After the study met its primary endpoint, the Food and Drug Administration approved voretigene neparvovec (Luxturna®) for use in RPE65-associated inherited retinal diseases.Keywords: gene therapy, inherited retinal diseases, Leber congenital amaurosis, Luxturna, RPE65, voretigene neparvovec, retinitis pigmentosa, retinaGao JHussain RMWeng CYDove Medical Pressarticlegene therapyinherited retinal diseasesleber congenital amaurosisluxturnarpe65voretigene neparvovecretinitis pigmentosaretinaOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 14, Pp 3855-3869 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	gene therapy inherited retinal diseases leber congenital amaurosis luxturna rpe65 voretigene neparvovec retinitis pigmentosa retina Ophthalmology RE1-994
spellingShingle	gene therapy inherited retinal diseases leber congenital amaurosis luxturna rpe65 voretigene neparvovec retinitis pigmentosa retina Ophthalmology RE1-994 Gao J Hussain RM Weng CY Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence
description	Jie Gao,1 Rehan M Hussain,2 Christina Y Weng1 1Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 2Retina Associates, Elmhurst, IL, USACorrespondence: Christina Y WengBaylor College of Medicine, Alkek Eye Center, 1977 Butler Blvd, Houston, TX 77030, USAEmail christina.weng@bcm.eduAbstract: Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed and showed similar diseased phenotypes to their human counterparts. Proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including electroretinograms, pupillary light responses, and object avoidance behaviors. Positive results in animal models led to Phase 1 human studies using adeno-associated viral vectors. Results in these initial human studies also showed positive impact on visual function and acceptable safety. A landmark Phase 3 study was then conducted by Spark Therapeutics using a dose of 1.5 x1011 vector genomes after dose-escalation studies confirmed its efficacy and safety. Multi-luminance mobility testing was used to measure the primary efficacy endpoint due to its excellent reliability in detecting the progression of inherited retinal diseases. After the study met its primary endpoint, the Food and Drug Administration approved voretigene neparvovec (Luxturna®) for use in RPE65-associated inherited retinal diseases.Keywords: gene therapy, inherited retinal diseases, Leber congenital amaurosis, Luxturna, RPE65, voretigene neparvovec, retinitis pigmentosa, retina
format	article
author	Gao J Hussain RM Weng CY
author_facet	Gao J Hussain RM Weng CY
author_sort	Gao J
title	Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence
title_short	Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence
title_full	Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence
title_fullStr	Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence
title_full_unstemmed	Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence
title_sort	voretigene neparvovec in retinal diseases: a review of the current clinical evidence
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/6274fcbff62d431f9b72397dcc8d7d15
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Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence

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