Development of a drug discovery platform for human islets

描述（由申请人提供）：糖尿病和糖尿病相关的合并症是流行病的比例和巨大的负担，我们的医疗保健系统。尽管在确定1型和2型糖尿病的致病因素和分子机制方面取得了重大进展，但确定有效的治疗方式仍然是一个巨大的挑战。迫切需要新的方法和工具来加速研究和开发其他疗法。虽然机制是不同的，在1型和2型糖尿病都有胰腺？细胞或？细胞功能，导致胰岛素产生完全或显著减少。人类胰岛是目前最具生理相关性的系统，用于检查调节胰岛素产生/分泌的潜在治疗剂，以及调节？细胞生物技术和制药公司迫切需要新的合同研究平台和工具，以加速其需要人类胰岛的药物开发计划。第一阶段申请的里程碑是成功的，包括开发高通量药物发现平台，使用“正常”和诱导疾病状态模型进行筛选。在当前的第2阶段应用中，我们将专注于这些平台的自然进展，包括用于研究的新型3D胰岛微组织（假胰岛）的商业化，建立额外的基于胰岛的测定，包括定量高含量成像（QHCI）平台的实施，以及使用小型化合物库筛选最终验证当前用于合同研究服务的HT测定。这些产品和服务是新颖的，是学术和制药机构迫切需要的，具有巨大的商业潜力。

DESCRIPTION (provided by applicant): Diabetes and diabetes-related co-morbidities are at epidemic proportions and an enormous burden to our healthcare system. Although there has been significant progress in defining the causative factors and molecular mechanisms involved in both type 1 and type 2 diabetes, it remains an overwhelming challenge to identify efficacious therapeutic modalities. Novel approaches and tools to accelerate research and development of additional therapeutics are urgently needed. Although the mechanisms are distinct, in both type 1 and type 2 diabetes there is a loss of pancreatic???cells or ?-cell function, resulting in a complete or significant reduction in insulin production. Human islets are currently the most physiologically relevant system for the examination of potential therapeutics that modulate the insulin production/secretion, and factors that regulate growth and apoptosis of ?-cells. Biotech and pharmaceutical companies are in urgent need of novel contract research platforms and tools to accelerate their drug development programs that require human islets. The milestones of the Phase 1 application were successful and included the development of high throughput drug discovery platforms using "normal" and induced disease state models for screening purposes. In the current phase 2 application we will focus on the natural progression of these platforms which include the commercialization of novel 3D islet microtissues (pseudoislets) for research, establishing additional islet-based assays including, implementation of a quantitative high content imaging (QHCI) platform and finally validation of the current HT assays for contract research services using a small compound library screen. These products and services are novel and urgently needed by academic and pharmaceutical institutes; there is significant commercial potential.