iPS cell enabled therapy for geographic atrophy

描述(由申请人提供)：CalCyte Treateutics Inc.的一个具体重点和专业知识是开发和应用小分子驱动(即化学定义的)基于干细胞的疗法来治疗年龄相关性黄斑变性(AMD)引起的地理萎缩(GA)。AMD影响着全球3000-5000万人和美国的1000万人1。它是三大洲不可逆转失明的主要原因，占美国每年510亿美元失明成本的最大份额。预计到2020年，由于人口老龄化，流行率将翻一番，这将夸大这些人和经济上的损失。AMD的严重视力丧失是由于脉络膜新生血管(CNV)、异常血管侵入视网膜或GA、视网膜色素上皮(RPE)、光感受器和脉络膜毛细血管的凋亡性丢失。在CNV发病机制的分子理解方面取得了重大进展，导致了FDA批准的视力改善疗法。相比之下，GA的发病机制仍然模糊不清，目前还没有FDA批准的疗法来治疗美国100万已经患有GA的人和数百万面临风险的人。在这项建议中，我们建议开发化学定义的方法，将人诱导的多能干细胞分化为视网膜色素上皮(RPE)细胞。这项工作将为GA患者的自体植入治疗奠定基础。 公共卫生相关性：AMD影响全球3000-5000万人和美国1000万人1。它是三大洲不可逆转失明的主要原因，占美国每年510亿美元失明成本的最大份额。预计到2020年，由于人口老龄化，流行率将翻一番，这将夸大这些人和经济上的损失。AMD的严重视力丧失是由于脉络膜新生血管(CNV)、异常血管侵入视网膜或GA、视网膜色素上皮(RPE)、光感受器和脉络膜毛细血管的凋亡性丢失。在CNV发病机制的分子理解方面取得了重大进展，导致了FDA批准的视力改善疗法。相比之下，GA的发病机制仍然模糊不清，目前还没有FDA批准的疗法来治疗美国100万已经患有GA的人和数百万面临风险的人。基于干细胞的疗法有望阻止并可能修复由于GA引起的退化。我们提出的研究将提供一种化学定义的分化和培养条件，可以直接转化为从自体iPS细胞生产人RPE细胞的GMP过程。这种包含综合发现和开发目标的转换方法将为GA产生新的有效治疗策略，GA是一种可怕的和未得到满足的医疗需求。

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.