iPS cell enabled therapy for geographic atrophy

iPS 细胞治疗地理萎缩

• 批准号: 7910752
• 负责人: BIN ZHANG
• 金额: $ 20.39万
• 依托单位: CALCYTE THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910752
• 关键词: Accounting; Affect; Age related macular degeneration; Apoptotic; Autologous; Blindness; Blood Vessels; Cell Differentiation process; Cell Therapy; Cells; Chemicals; Choroidal Neovascularization; Development; Economics; Engraftment; FDA approved; Growth Factor; Human; Medical; Methods; Molecular; Panthera leo; Pathogenesis; Patients; Photoreceptors; Prevalence; Principal Investigator; Procedures; Production; Research; Retina; Risk; Signal Pathway; Stem cells; Structure of retinal pigment epithelium; Therapeutic; Translating; United States; Vision; Visual Fields; Work; aging population; cost; cytokine; geographic atrophy; improved; in vitro testing; in vivo; induced pluripotent stem cell; method development; monolayer; novel; programs; public health relevance; repaired; small molecule; stem; translational approach

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.

描述（由申请人提供）：CalCyte Therapeutics Inc.的一个特定重点和专业知识。是开发和应用小分子驱动的（即化学定义的）基于干细胞的疗法来治疗来自年龄相关性黄斑变性（AMD）的地图状萎缩（GA）。AMD影响全球3000万至5000万人，美国1000万人1。它是三大洲不可逆失明的主要原因，在美国每年510亿美元的失明费用中占最大份额。到2020年，由于人口老龄化，预计患病率将翻一番，这将夸大这些人力和经济损失。来自AMD的严重视力丧失由脉络膜新生血管形成（CNV）、异常血管对视网膜的侵入或由GA、视网膜色素上皮（RPE）、光感受器和脉络膜毛细血管的凋亡损失引起。CNV发病机制的分子理解的重大进展导致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，并且对于美国已经患有GA的100万人和处于风险中的数百万人没有FDA批准的疗法。在这个提议中，我们建议开发化学定义的方法，用于将人诱导多能干（iPS）细胞分化为视网膜色素上皮（RPE）细胞。这项工作将为GA患者的自体移植治疗奠定基础。 公共卫生相关性：AMD影响全球3000 - 5000万人，美国1000万人1。它是三大洲不可逆失明的主要原因，在美国每年510亿美元的失明费用中占最大份额。到2020年，由于人口老龄化，预计患病率将翻一番，这将夸大这些人力和经济损失。来自AMD的严重视力丧失由脉络膜新生血管形成（CNV）、异常血管对视网膜的侵入或由GA、视网膜色素上皮（RPE）、光感受器和脉络膜毛细血管的凋亡损失引起。CNV发病机制的分子理解的重大进展导致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，美国有100万人已经患有GA，还有数百万人处于危险之中，没有FDA批准的治疗方法。基于干细胞的治疗有很大的希望停止并可能修复由于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程序。这种包括综合发现和开发目标的转化方法将为GA产生新的有效的治疗策略，这是一种迫切且未满足的医疗需求。