ArticleInvestigative ophthalmology & visual science2026
Combined Expression of hRdCVF and hRdCVFL Through AAV-Mediated Delivery for the Treatment of Retinitis Pigmentosa.
Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05748873 (A Phase I/II Study to Assess the Safety and Tolerability of a Single Subretinal Administration of SPVN06 Gene Therapy in Subjects With Rod-Cone Dystrophy), which is not on this map. Not yet cited in PubMed.
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A Phase I/II Study to Assess the Safety and Tolerability of a Single Subretinal Administration of SPVN06 Gene Therapy in Subjects With Rod-Cone Dystrophy (RCD)
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17 authors.
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Abstract
Purpose: Retinitis pigmentosa (RP) is an inherited retinal degeneration that progresses from rod to cone degeneration. Several gene-independent adeno-associated virus (AAV)-based strategies have revealed a partial restauration of RP using AAV vectors coding for either rod-derived cone viability factor (RdCVF) or its long form (RdCVFL). The nucleoredoxin-like 1 gene (NXNL1) encodes two proteins, the short isoform RdCVF and the long isoform (RdCVFL). RdCVF acts by stimulating aerobic glycolysis to sustain cone outer segment renewal, and RdCVFL is thought to modulate oxidative stress. In prior studies, we analyzed the structural and functional effect of each isoform delivered independently through co-injection of two vectors carrying each. Here, we aimed to maintain visual function by performing a unilateral subretinal injection of a single AAV vector encoding both human isoforms, hRdCVF and hRdCVFL, in an RP mouse model. Methods: The therapeutic effect of AAV-hRdCVF/hRdCVFL versus AAV-hRdCVF was evaluated using a visual function test on rd10 mice followed by automated cone counting and measurement of lipid peroxidation. Results: A significant visual preservation using AAV-hRdCVF/hRdCVFL versus AAV-hRdCVF was observed from 28 days post-injection, as shown by delayed visual loss, increased cone density, and reduced lipid peroxidation. Conclusions: This study revealed that both proteins encoded by NXNL1 are essential for gene-independent RP treatment and that combining RdCVF and RdCVFL delivery with a single AAV vector yields a more substantial photoreceptor-protective effect. This functional proof of concept supports the ongoing gene therapy phase 1/2 trial Promising ROd-cone DYstrophy Gene therapY (PRODYGY, NCT05748873).
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