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

Journal article

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.

Authors: Cehajic-Kapetanovic, J; Xue, K; Martinez-Fernandez de la Camara, C; Nanda, A; Davies, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Medicine
• Volume: 26
• Issue: 3
• Pages: 354-359
• Place of publication: United States
• Publication date: 2020-02-24
• Acceptance date: 2020-01-10
• DOI: 10.1038/s41591-020-0763-1
• EISSN: 1546-170X
• ISSN: 1078-8956
• Pmid: 32094925
• Language: English
• Keywords: mutation; middle aged; retina; eye proteins; retinitis pigmentosa; young adult; genetic diseases, x-linked; genetic therapy; FFR