Novel Methodology for Identification of Senolytics that Reduce Age-related Disease and Dysfunction

鉴定可减少年龄相关疾病和功能障碍的 Senolytics 的新方法

• 批准号: 9792234
• 负责人: Anthony John Donato
• 金额: $ 43.4万
• 依托单位: RECURSION PHARMACEUTICALS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9792234
• 关键词: Affect; Age; Aging; American; Biological; Cardiovascular Diseases; Cell Aging; Cells; Chronic Disease; Complex; Development; Disease; Drug Screening; Exposure to; Functional disorder; Healthcare; Human; Image; Image Analysis; Inflammatory; Methodology; Modeling; Morphology; Mus; Pain; Pathology; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Phase; Risk; Small Business Innovation Research Grant; Stress; System; Tissues; Tumor Initiators; age related; cell type; drug discovery; experience; fluorescence imaging; healthspan; improved; machine learning algorithm; mortality; mouse model; novel; prevent; programs; public health relevance; senescence; tool

DESCRIPTION (provided by applicant): Chronic diseases of aging account for a significant proportion of healthcare spending and result in a painful and limiting existence for many tens of millions of Americans and hundreds of millions of people around the world. Recursion Pharmaceuticals has developed a drug discovery platform that re-purposes known drugs for the treatment of such diseases. The platform consists of high content fluorescent image analysis using machine-learning algorithms to identify relevant and on-target changes induced in human cells in which diseases and treatments have been modeled. This system has been adapted to screen for drugs which may preferentially destroy senescent cells, as this may result in improved tissue function and decreases in pathology and mortality related to aging. In this SBIR fast-track proposal we will: PHASE I Identify a morphological profile of senescence in a variety of human cell types. Progression to Phase II will depend on our ability to demonstrate the power of our morphological approach to identify senescent cells independent of any known senescent markers. PHASE II Identify known drugs which preferentially destroy senescent cells, without affecting healthy cells, as identified by morphometric means. Evaluate the efficacy of identified senolytic agents in a variety of tissue function and health-span models in mice. *Evaluate the effect of identified senolytic agents in a murine model of age-associated cardiovascular disease. Recursion Pharmaceuticals has the experience, tools, and drive to execute this Phase I/Phase II Fast-track SBIR proposal, and to accelerate commercial development of any compounds we identify as a result.

描述（由申请人提供）：慢性衰老疾病占医疗保健支出的很大一部分，给数千万美国人和世界各地数亿人带来痛苦和限制。 Recursion Pharmaceuticals 开发了一个药物发现平台，可以重新利用已知药物来治疗此类疾病。该平台由高内涵荧光图像分析组成，使用机器学习算法来识别在疾病和治疗已建模的人类细胞中诱导的相关和目标变化。该系统已适应筛选可能优先破坏衰老细胞的药物，因为这可能会改善组织功能并降低与衰老相关的病理学和死亡率。在这个 SBIR 快速提案中，我们将： 第一阶段 识别多种人类细胞类型的衰老形态学特征。进入第二阶段将取决于我们是否有能力证明我们的形态学方法能够独立于任何已知的衰老标记来识别衰老细胞。 第二阶段 识别已知的药物，这些药物优先破坏衰老细胞，而不影响健康细胞，如通过形态测量手段识别的。 评估已确定的抗衰老药物在小鼠各种组织功能和健康范围模型中的功效。 *评估已确定的抗衰老药物在与年龄相关的心血管疾病的小鼠模型中的作用。 Recursion Pharmaceuticals 拥有执行这一第一阶段/第二阶段快速 SBIR 提案的经验、工具和动力，并加速我们由此确定的任何化合物的商业开发。