Retinal gene therapy in X-linked retinitis pigmentosa caused by mutations in RPGR: Results at 6 months in a first in human clinical trial

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(1,2,3,4,5,6). Here we report the first in human Phase I/II dose escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene(7) in 18 patients up to 6 months follow-up (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 significant safety concerns following subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8.coRPGR)(8) meeting the pre-specified primary endpoint. Visual field improvements beginning at one month and maintained to the last point of follow-up were observed in six patients.