This causes cone function to degenerate, leading to cell death and blindness. Identification of RdCVF2, a gene paralogous to RdCVF. PMCID: PMC7084304 PMID: 32120883. ... the Phase I / II clinical trial is planned for 2020. We describe in detail all the steps of this translational program, from the design of the drug, its production, biological validation, and analytical and preclinical qualification required for a future clinical trial that would, if successful, provide a treatment for this incurable disease. The mouse RdCVF gene is located on chromosome 8 and contains three exons (Figure 1, panel a).The RdCVF-S splice variant is composed of a single exon in which the coding sequence is the same as the first exon of the long form extended by one codon followed by a stop codon (TGA) and finally a 3' untranslated region (UTR). Morphology of cones in the RdCVF untreated and treated retinas. ... RdCVF is naturally secreted by rods, the retinal cells that provide night and peripheral vision. Because the secondary loss of cones in retinitis pigmentosa (RP) leads to blindness, the administration of RdCVF is a promising therapy for this untreatable neurodegenerative disease. Three decades of vision research culminated in the first gene therapy trials for Leber congenital amaurosis (LCA) caused by RPE65 mutations, … Gene therapy-mediated expression of RdCVF may therefore be an effective treatment in delaying retinal degeneration. Morphology of cones in the RdCVF untreated and treated retinas. Figure S1. The truncated form (RdCVF) is a thioredoxin-like protein secreted by rods that promotes cone survival, while the full-length isoform (RdCVFL), which contains a thioredoxin fold, is involved in oxidative signaling and protection against hyperoxia. The identification of one mechanism that causes vision loss in inherited degenerative retinal disorders revealed a new signaling molecule that represents a potential therapy for these currently untreatable diseases. Fovea is conducting further studies to produce RdCVF and plans to start clinical trials in 2009. About Retinitis Pigmentosa RP is a long lasting disease that slowly evolves towards irreversible blindness. RdCVF protein (109 amino acids) was chemically synthesized (>90% purity) and refolded ().The activity of the synthesized protein was measured using an in vitro cone-enriched culture system. Meanwhile, recent Phase I clinical trials have demonstrated safety and efficacy in restoring vision in Type 2 Leber's Congenital Amaurosis (LCA2), using AAV2-mediated gene replacement of the RPE65 gene. Rod-derived cone viability factor (RdCVF) is an inactive thioredoxin secreted by rod photoreceptors that protects cones from degeneration. Fovea is conducting further studies to produce RdCVF and plans to start clinical trials in 2009. A clinical trial for the treatment, designed to preserve cone photoreceptors, is planned in the US and Europe in 2020. A clinical trial for the treatment, designed to preserve cone photoreceptors, is planned in the US and Europe in 2020. When there is a mutation in the rods, RdCVF is no longer present. Several cones scanned by confocal microscope display smaller, ellipse tip area and longer outer segment in the RdCVF treated retina (A-D), differing from larger tip area and shorter segment in the non-treated retina (E-H). RdCVF, discovered by team 1, and developed by team 5, has been granted by the EMEA and FDA the Orphan Status. In RP, the blindness occurs over a 15-year period and starts between the ages of 20 and 30.