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

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

Research output: Contribution to journalLetter

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.

Original languageEnglish (US)
JournalNature medicine
DOIs
StateAccepted/In press - Jan 1 2020

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., Nanda, A., Davies, A., Wood, L. J., Salvetti, A. P., Fischer, M. D., Aylward, J. W., Barnard, A. R., Jolly, J. K., Luo, E., Lujan, B. J., Ong, T., Girach, A., Black, G. C. M., Gregori, N. Z., Davis, J. L., Rosa, P. R., ... MacLaren, R. E. (Accepted/In press). Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nature medicine. https://doi.org/10.1038/s41591-020-0763-1