Preclinical studies show that fenretinide reduces the expression of vascular endothelial growth factor (VEGF) isoforms. These proteins are known to cause aberrant growth of leaky vessels within the retina and have been implicated in severe vision loss in patients with CNV. Fenretinide was also found to upregulate the expression of complement factor H, a potent inhibitor of the inflammatory pathway. Dysfunction or deficits in complement factor H are known to significantly increase risk for development of CNV. This preclinical data suggests that the anti-angiogenic and anti-inflammatory properties of fenretinide may underlie the reduced incidence of CNV observed in the clinical trial.
The accumulation of retinol (vitamin A)-derived toxins in the eye is believed to be a significant risk factor for the development of GA. The ability of fenretinide to reduce the delivery of retinol to the eye, and therefore reduce accumulation of these toxins, is thought to mitigate this risk. Analysis of GA lesion growth by color fundus photography showed a trend for slowing of lesion growth in patients receiving fenretinide. This trend was particularly evident in patients in the 300 mg dose group who had substantial reductions in serum retinol and its carrier protein, retinol binding protein (RBP). Data from the 300 mg dose group demonstrated a reduction in median lesion growth when RBP and retinol levels were reduced by more than 50 percent. This finding supports the proof of concept that reduction of circulating RBP and retinol reduces lesion growth in patients with GA.
Full analysis of all lesion size measurements is ongoing. The complete data will be presented later this year at the annual meeting of the American Academy of Ophthalmology.
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|SOURCE ReVision Therapeutics Inc.|
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