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Development of a drug discovery platform for human islets

开发人类胰岛药物发现平台

基本信息

批准号：
8642796
负责人：
BENJAMIN M BUEHRER
金额：
$ 107.27万
依托单位：
ZEN-BIO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8642796
关键词：
Age Apoptosis Automation Biological Assay Businesses C-Peptide CCL2 gene Camptothecin Cell Count Cell Survival Cell physiology Cells Client Comorbidity Contract Services Contracts Development Diabetes Mellitus Disease Epidemic GCG gene Gene Expression Glucagon Goals Growth Healthcare Systems Human Hypoxia IL6 gene IL8 gene Image Inflammatory Institutes Insulin Interleukin-1 Islet Cell Libraries Maintenance Marketing Measures Modality Modeling Molecular Molecular Profiling Pancreas Performance Pharmacologic Substance Phase Preparation Production Protocols documentation Quality Control Reagent Research Research Contracts Services Shipping Ships Signal Transduction Somatostatin Staurosporine System Therapeutic Validation base cell preparation commercialization cytokine diabetes mellitus therapy drug development drug discovery factor C high throughput screening innovation islet model development novel novel strategies programs public health relevance research and development screening small molecule small molecule libraries therapy development tool type I and type II diabetes

项目摘要

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.

描述（由申请人提供）：糖尿病和糖尿病相关合并症已成为流行病，给我们的医疗保健系统带来了巨大负担。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已经取得了重大进展，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其他疗法的研究和开发。尽管机制不同，但在 1 型和 2 型糖尿病中，胰腺细胞或 β 细胞功能均丧失，导致胰岛素产生完全或显着减少。人类胰岛是目前用于检查调节胰岛素产生/分泌的潜在疗法以及调节β细胞生长和凋亡的因子的最具生理相关性的系统。生物技术和制药公司迫切需要新颖的合同研究平台和工具来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，包括使用“正常”和诱导疾病状态模型进行筛选的高通量药物发现平台的开发。在当前的第 2 阶段应用中，我们将重点关注这些平台的自然进展，其中包括用于研究的新型 3D 胰岛微组织（伪胰岛）的商业化，建立其他基于胰岛的测定，包括实施定量高内涵成像 (QHCI) 平台，最后使用小型化合物库筛选验证当前用于合同研究服务的 HT 测定。这些产品和服务新颖，是学术和制药机构迫切需要的；具有巨大的商业潜力。