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Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR
Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR

Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.

1078-8956
354–359
Cehajic-Kapetanovic, Jasmina
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Xue, Kanmin
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Martinez-Fernandez de la Camara, Cristina
21a152c0-5f72-4d74-8260-59718a0fe789
Nanda, Anika
5366dbf2-d4b0-4b9f-9026-7ed20601a396
Davies, Alexandra
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Wood, Laura J.
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Salvetti, Anna Paola
cdfe6548-241e-4f70-ac39-a0a5cf3b4814
Fischer, M. Dominik
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Aylward, James W.
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Barnard, Alun R.
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Jolly, Jasleen K.
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Luo, Edmond
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Lujan, Brandon J.
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Ong, Tuyen
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Girach, Aniz
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Black, Graeme C.M.
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Gregori, Ninel Z.
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Davis, Janet L.
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Rosa, Potyra R.
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Lotery, Andrew J.
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Lam, Byron L.
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Stanga, Paulo E.
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MacLaren, Robert E.
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Cehajic-Kapetanovic, Jasmina
58f9cc83-5a9c-419b-9532-709367cc319e
Xue, Kanmin
161b105d-40c3-41b7-8db9-f5af21a52335
Martinez-Fernandez de la Camara, Cristina
21a152c0-5f72-4d74-8260-59718a0fe789
Nanda, Anika
5366dbf2-d4b0-4b9f-9026-7ed20601a396
Davies, Alexandra
652d9222-f87a-4a76-bdf3-98e8ecb248b5
Wood, Laura J.
700b14b7-620d-4b39-b856-382b23fe94f2
Salvetti, Anna Paola
cdfe6548-241e-4f70-ac39-a0a5cf3b4814
Fischer, M. Dominik
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Aylward, James W.
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Barnard, Alun R.
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Jolly, Jasleen K.
3196d568-3730-4b67-8418-9b1ef271aba7
Luo, Edmond
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Lujan, Brandon J.
dc50370a-c332-4e85-ab5e-b009de2241e5
Ong, Tuyen
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Girach, Aniz
f68da9d5-fc8c-49c6-a552-25c7e8504ad1
Black, Graeme C.M.
fa6e5597-81de-46f6-b7b4-d2d712cc84a9
Gregori, Ninel Z.
37aca857-3f05-463c-8d23-ebddd32da395
Davis, Janet L.
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Rosa, Potyra R.
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Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Lam, Byron L.
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Stanga, Paulo E.
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MacLaren, Robert E.
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Cehajic-Kapetanovic, Jasmina, Xue, Kanmin, Martinez-Fernandez de la Camara, Cristina, Nanda, Anika, Davies, Alexandra, Wood, Laura J., Salvetti, Anna Paola, Fischer, M. Dominik, Aylward, James W., Barnard, Alun R., Jolly, Jasleen K., Luo, Edmond, Lujan, Brandon J., Ong, Tuyen, Girach, Aniz, Black, Graeme C.M., Gregori, Ninel Z., Davis, Janet L., Rosa, Potyra R., Lotery, Andrew J., Lam, Byron L., Stanga, Paulo E. and MacLaren, Robert E. (2020) Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nature Medicine, 26 (3), 354–359. (doi:10.1038/s41591-020-0763-1).

Record type: Letter

Abstract

Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.

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More information

Accepted/In Press date: 10 January 2020
e-pub ahead of print date: 24 February 2020
Published date: March 2020

Identifiers

Local EPrints ID: 442007
URI: http://eprints.soton.ac.uk/id/eprint/442007
ISSN: 1078-8956
PURE UUID: a0f2c58b-efc7-4a91-853c-3b3bab4405ce
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 03 Jul 2020 16:38
Last modified: 06 Jun 2024 01:41

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Contributors

Author: Jasmina Cehajic-Kapetanovic
Author: Kanmin Xue
Author: Cristina Martinez-Fernandez de la Camara
Author: Anika Nanda
Author: Alexandra Davies
Author: Laura J. Wood
Author: Anna Paola Salvetti
Author: M. Dominik Fischer
Author: James W. Aylward
Author: Alun R. Barnard
Author: Jasleen K. Jolly
Author: Edmond Luo
Author: Brandon J. Lujan
Author: Tuyen Ong
Author: Aniz Girach
Author: Graeme C.M. Black
Author: Ninel Z. Gregori
Author: Janet L. Davis
Author: Potyra R. Rosa
Author: Byron L. Lam
Author: Paulo E. Stanga
Author: Robert E. MacLaren

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