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

• Published in: Nature medicine Vol. 26; no. 3; pp. 354 - 359
• Main Authors: 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, MacLaren, Robert E
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2020
• Subjects: Acuity; Adult; Care and treatment; Complications and side effects; Degeneration; Eye Proteins - genetics; Eye Proteins - therapeutic use; Gene mutations; Gene therapy; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - therapy; Genetic Therapy; Guanosine triphosphatases; Health aspects; Humans; Middle Aged; Mutation; Mutation - genetics; Patient outcomes; Patients; Retina; Retina - pathology; Retina - physiopathology; Retinal degeneration; Retinitis; Retinitis pigmentosa; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - physiopathology; Retinitis Pigmentosa - therapy; Safety; Steroids; Visual acuity; Visual field; Visual fields; Visual perception; Young Adult; Young adults; United Kingdom
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-020-0763-1

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.