SparingVision is born to develop a gene therapy loaded with the two synergistic isoforms of NXNL1 (RdCVF and RdCVFL) in a single vector.

A synergistic effect of RdCVF and RdCVFL is demonstrated (Byrne et al, 2015).

A gene therapy project between Institut de la Vision (Paris, France) and University of Berkeley (California, USA) is begun, seeking to restore the natural neuroprotective effect of rods for cones via the secretion of RdCVF in patients suffering from retinitis pigmentosa at a stage where they have lost rod functionality, leading to loss of night and peripherical vision.

Thierry Léveillard demonstrates that the protective mechanism of RdCVF is mediated via the supply of glucose to cones and a specific metabolic pathway: aerobic glycolysis (Ait-Ali et al, 2015).

A longer isoform (RdCVFL) of NXNL1 is characterized. Produced by the cones (and the rods) it protects the cones via an anti-oxidative mechanism [Cronin et al, 2010, Elachouri] et al, 2015, Wei et al, 2015).

The same academic group demonstrates the efficiency of re-administering the factor in various mutants affected with rod-cone dystrophies (Yang et al,2009).

Thierry Léveillard and José-Alain Sahel identify the signal: it is characterized as a product of NXNL1 (Nucleoredoxin-like 1), a gene coding for two proteins: the trophic factor and a thioredoxin-like protein (Léveillard et al, 2004)

José-Alain Sahel and his academic team demonstrate that cone maintenance is dependent on a trophic signal/factor secreted by rods (Mohand-Said et al, 1998) tentatively named Rod-derived Cone Viability Factor (RdCVF) (Sahel et al, 2001, Mohand-Said et al, 2001).

Studies conducted by José-Alain Sahel (with Saddek Mohand-Said et David Hicks) demonstrate that cone disappearance is a collateral damage or a side effect from the disappearance of rods and that this mechanism is not a direct effect of the causative mutation (Sahel et al, 1996, Mohand-Said et al, 1997, 2000).