Age-related macular degeneration (AMD) stands as a predominant cause of blindness, impacting the macula and resulting in central vision loss due to retinal damage. This affliction, prevalent in individuals over 55 years old, affected 196 million people globally in 2020, with an estimated economic burden of $343 billion, encompassing $255 billion in direct healthcare costs. The macula, a critical region for visual acuity, relies on the intricate interplay of photoreceptors and retinal pigmented epithelium (RPE) cells. In the normal eye, RPE cells play a pivotal role in supporting photoreceptor function, maintaining the health of the retina, and facilitating optimal visual perception.
However, in AMD, a disease that progressively debilitates vision, photoreceptors and RPE cells undergo degeneration during aging. The prevailing standard of care involves periodic injections of anti-VEGF medications like ranibizumab (Lucentis), aflibercept (Eylea), and brolucizumab (Beovu), administered every 1-3 months. While these treatments impede disease progression, they fall short in restoring lost vision and entail side effects such as ocular bleeding.
Within the context of an ERC Starting project, the principal investigator unveiled a novel method that can potentially delay AMD by enhancing the function of RPE cells—a breakthrough in AMD treatment. The proposed strategy involves rejuvenation through partial reprogramming, a technique the results of which indicate both safety and efficacy in rejuvenating mouse fibroblasts while improving their function.
In this application, our focus shifts to RPE studies to pave the way for the implementation of our innovative approach embodied in the envisioned product, "I-SEE." "I-SEE" leverages the discovery of a trophoblast stem cell-specific (TSC) combination of factors, proven successful in reprogramming cells, to drive the rejuvenation and improved function of aging RPE cells. Our plan includes meticulous calibration of the expression of TSC reprogramming factors in RPE cells, followed by testing for rejuvenation and improved function in AMD mouse models.
The culmination of our efforts, "I-SEE," is built upon a PCT patent Application No. 63/210,030, featuring a cocktail of mRNA molecules directly applied to the eye. This innovative approach aims to provide the first AMD treatment capable of delaying vision lost, marking a significant advancement in the field.
