Phase 1/2a Clinical Trial Protocol for Lentiviral Vector-Based Retinal Gene Therapy to Slow the Progression of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies (IRDs) that cause progressive rod and cone photoreceptor cell death. Currently, there is no treatment for RP, and it is a significant cause of blindness worldwide. Neuroprotective retinal gene therapy is a promising therapeutic strategy applicable to various causative genes. We have developed a third-generation lentiviral vector based on a simian immunodeficiency virus from African green monkeys (SIVagm), which allows efficient gene transfer into the retinal pigment epithelium via subretinal injection. In preclinical studies, we used the human gene encoding pigment epithelium-derived factor (PEDF), a potent neuroprotective molecule, and the SIVagm vector encoding human PEDF (SIV-hPEDF) significantly delayed retinal degeneration in rodent models of RP and achieved stable, safe, and long-term transgene expression over 5 years in nonhuman primates. Based on these findings, we conducted a Phase 1/2a investigator-initiated clinical trial using SIV-hPEDF to slow the disease progression and prevent blindness in RP patients, and we here outline the study protocol.