Spatial and temporal resolution of the photoreceptors rescue dynamics after treatment with voretigene neparvovec.
diagnostic tests/investigation
dystrophy
genetics
retina
treatment other
Journal
The British journal of ophthalmology
ISSN: 1468-2079
Titre abrégé: Br J Ophthalmol
Pays: England
ID NLM: 0421041
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
30
10
2020
revised:
22
12
2020
accepted:
28
12
2020
pubmed:
22
1
2021
medline:
25
5
2022
entrez:
21
1
2021
Statut:
ppublish
Résumé
Voretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic Seven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic All except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R The presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.
Sections du résumé
BACKGROUND
Voretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic
METHODS
Seven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic
RESULTS
All except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R
CONCLUSIONS
The presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.
Identifiants
pubmed: 33472769
pii: bjophthalmol-2020-318286
doi: 10.1136/bjophthalmol-2020-318286
pmc: PMC9132865
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
831-838Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: DF is or has been on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: Adelphi Values, Advent France Biotechnology, Alphasights, Atheneum, Axiom Healthcare Strategies, Biogen, Decision Resources, Dialectica, EyeServ, Frontera Therapeutics, Janssen Research & Development, Navigant, Novartis, Roche, RegenxBio, Sirion and STZeyetrial. DF is director of Fischer Consulting Limited and holds a patent (50%) on a gene therapy product for X-linked Retinitis Pigmentosa. DF is the lead investigator of the global (ex-US) post-authorisation, multicentre, multinational, longitudinal, observational safety registry study for patients treated with voretigene neparvovec (CLTW888A12401) and a part of the data reported here are included in that study. EZ is or has been on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: SMERUD, Atheneum, Axiom Healthcare strategies, Biogen, Decision Resources, Janssen Research & Development, Navigant, RegenxBio, ProQR, Gyroscope, Astellas and STZ eyetrial. KaS has received grants and/or travel reimbursement from Novartis, ProQR and ORA. SK and FW received personal fees from Novartis. BaW and TP received other support from Novartis.
Références
Lancet. 2016 Aug 13;388(10045):661-72
pubmed: 27375040
Cold Spring Harb Perspect Med. 2015 Jan 29;5(9):a017285
pubmed: 25635059
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15112-7
pubmed: 18809924
Transl Vis Sci Technol. 2019 Nov 20;8(6):19
pubmed: 31788348
Ophthalmology. 2013 Jun;120(6):1283-91
pubmed: 23474247
F1000Res. 2018 May 23;7:
pubmed: 29899971
Ophthalmologe. 2020 Jan;117(Suppl 1):16-24
pubmed: 31089806
N Engl J Med. 2008 May 22;358(21):2240-8
pubmed: 18441370
Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):1122-1131
pubmed: 30901388
Nature. 1991 Aug 29;352(6338):798-800
pubmed: 1881435
Biomed Tech (Berl). 2018 Nov 27;63(6):729-734
pubmed: 29369809
Lancet. 2009 Nov 7;374(9701):1597-605
pubmed: 19854499
Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4293-9
pubmed: 11095629
Ophthalmology. 2019 Sep;126(9):1273-1285
pubmed: 31443789
Ophthalmology. 2016 Jul;123(7):1606-20
pubmed: 27102010
Nat Genet. 1998 Dec;20(4):344-51
pubmed: 9843205
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4759-65
pubmed: 17898302
Transl Vis Sci Technol. 2020 May 11;9(6):5
pubmed: 32821502
J Biol Chem. 1993 Jul 25;268(21):15751-7
pubmed: 8340400
Mol Ther. 2010 Mar;18(3):643-50
pubmed: 19953081
Prog Retin Eye Res. 2011 Mar;30(2):115-28
pubmed: 21111842
Transl Vis Sci Technol. 2017 Aug 09;6(4):15
pubmed: 28798898
Ophthalmologica. 2021;244(5):396-407
pubmed: 32805733
Front Neurol. 2019 Feb 22;10:129
pubmed: 30853933
Arch Ophthalmol. 2012 Jan;130(1):9-24
pubmed: 21911650
Hum Gene Ther. 2018 Dec;29(12):1428-1437
pubmed: 29869534
Ophthalmology. 2004 Aug;111(8):1585-94
pubmed: 15288992
Lancet. 2017 Aug 26;390(10097):849-860
pubmed: 28712537
Invest Ophthalmol Vis Sci. 2002 May;43(5):1604-9
pubmed: 11980880
N Engl J Med. 2008 May 22;358(21):2231-9
pubmed: 18441371
Nat Genet. 1997 Oct;17(2):194-7
pubmed: 9326941