iPS cell enabled therapy for geographic atrophy

DESCRIPTION (provided by applicant): One specific focus and expertise of CalCyte Therapeutics Inc. is to develop and apply small molecule driven (i.e. chemically defined), stem cell based therapy to treat geographic atrophy (GA) from age-related macular degeneration (AMD). AMD affects 30-50 million people worldwide and 10 million people in the United States1. It is the leading cause of irreversible blindness on three continents and accounts for a lion's share of the annual 51 billion cost of blindness in the United States. These human and economic tolls will be exaggerated by the expected doubling of prevalence by 2020 due to the aging population. Severe vision loss from AMD results from choroidal neovascularization (CNV), the invasion of the retina by abnormal blood vessels, or from GA, the apoptotic loss of retinal pigmented epithelium (RPE), photoreceptors and choriocapillaris. Significant advances in the molecular understanding of CNV pathogenesis have led to an FDA-approved vision-improving therapy. In contrast, GA pathogenesis is still nebulous and there are no FDA- approved therapies for the 1 million people in the United States who already have GA and the millions more who are at risk. In this proposal, we propose to develop chemically defined methods for differentiation of human induced pluripotent stem (iPS) cells into retinal pigment epithelium (RPE) cells. This work will lay the ground for autologous engraftment treatment in GA patients. PUBLIC HEALTH RELEVANCE: AMD affects 30-50 million people worldwide and 10 million people in the United States1. It is the leading cause of irreversible blindness on three continents and accounts for a lion's share of the annual 51 billion cost of blindness in the United States. These human and economic tolls will be exaggerated by the expected doubling of prevalence by 2020 due to the aging population. Severe vision loss from AMD results from choroidal neovascularization (CNV), the invasion of the retina by abnormal blood vessels, or from GA, the apoptotic loss of retinal pigmented epithelium (RPE), photoreceptors and choriocapillaris. Significant advances in the molecular understanding of CNV pathogenesis have led to an FDA-approved vision-improving therapy. In contrast, GA pathogenesis is still nebulous and there are no FDA-approved therapies for the 1 million people in the United States who already have GA and the millions more who are at risk. Stem cell based therapy holds great promise to halt and possibly repair the degeneration due to GA. Our proposed research will provide a chemically defined differentiation and culture condition which can be directly translate into a GMP procedure for human RPE cell production from autologous iPS cells. This translational approach comprising integrated discovery and development aims will yield new and effective therapeutic strategies for GA, a dire and unmet medical need.