Translational Center for Alzheimer's Disease Target and Drug Discovery

阿尔茨海默病靶点和药物发现转化中心

• 批准号: 8849662
• 负责人: DOUGLAS R GALASKO
• 金额: $ 31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8849662
• 关键词: Address; Affect; Alzheimer' s Disease; Animal Model; Archives; Area; Attenuated; Autopsy; Basic Science; Biochemical; Bioinformatics; Biological; Biological Assay; Biological Markers; Biomedical Engineering; Biomedical Research; Biometry; Brain; California; Cataloging; Catalogs; Cell model; Cells; Clinical; Clinical Research; Collaborations; Collection; Communication; Coupled; Data; Data Set; Data Storage and Retrieval; Dementia; Development; Disease; Disease Progression; Drug Kinetics; Educational workshop; Engineering; Exercise; Failure; Fibroblasts; Foundations; Generations; Genetic Research; Genomics; Goals; Grant; Human; Human Resources; Institutes; Institution; Link; Medical; Medical Research; Medicine; Methods; Modeling; Network-based; Neurobiology; Neurons; Online Systems; Participant; Pathway Analysis; Patients; Pharmacodynamics; Pharmacologic Substance; Pharmacology; Phenotype; Preclinical Drug Evaluation; Prevention; Procedures; Process; Proteomics; Protocols documentation; Publishing; Reagent; Research; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; Resource Sharing; Resources; Staging; Stem Cell Research; System; Systems Biology; Systems Development; Technology; Testing; Therapeutic; Toxicology; Training; Training Programs; Training and Education; Transgenic Mice; Translational Research; animal data; brain tissue; cellular imaging; computer science; computerized data processing; data sharing; disorder control; drug development; drug discovery; graduate student; high throughput screening; human data; improved; induced pluripotent stem cell; innovation; longitudinal human study; mRNA Expression; metabolomics; mouse model; multidisciplinary; neuropathology; predictive modeling; prevent; public health relevance; small molecule libraries; stem cell technology; success; tool

 DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is the most common cause of dementia, a devastating disorder that affects over 35 million people worldwide. Our ultimate objective is to apply quantitative and systems pharmacology (QSP) approaches to AD drug discovery and development in order to deliver treatments capable of significantly attenuating the progression and/or preventing the disease. We will utilize this planning grant to integrate the necessary personnel, expertise and resources to assemble an infrastructure of cores across four San Diego medical research institutions (UCSD, the Salk Institute, the Scripps Research Institute and the Sanford Burnham Medical research Institute) and UCLA that are necessary for planning an AD Translational Center for Predictive Drug Development. This will be accomplished in part using a web-based platform that is currently under development (Systems Medicine Alzheimer's Research and Treatment or SMART) ://smart.ucsd.edu. Cataloging and integration of resources including cellular and animal models, reagents, chemical libraries of compounds, existing compounds in various stages of development, biosamples, postmortem brain tissue, methods such as high throughput screens and archiving and annotating of newly-generated multi-omics datasets (including existing data from cellular and animal models) as well as data from human longitudinal studies. A major focus will be the utilization of human iPSC (hiPSC) from extremely well phenotyped patients (including extreme phenotypes) to attempt to establish disease in a dish models. In addition we will capitalize on the local abundance of expertise in systems biology, biostatistics and bioinformatics bioengineering, pharmacology, neuropathology and clinical research to establish appropriate training programs in QSP for graduate students, medical trainees and postdoctoral scholars. Finally, we will identify processes to enable highly effective data sharing and establish strong collaborations with pharmaceutical companies.

 描述（由申请人提供）：阿尔茨海默病（AD）是痴呆症的最常见原因，这是一种破坏性疾病，影响全球超过3500万人。我们的最终目标是将定量和系统药理学（QSP）方法应用于AD药物发现和开发，以提供能够显著减缓进展和/或预防疾病的治疗。我们将利用这一规划补助金整合必要的人员，专业知识和资源，以组装在四个圣地亚哥医学研究机构（加州大学圣地亚哥分校，索尔克研究所，斯克里普斯研究所和桑福德伯纳姆医学研究所）和加州大学洛杉矶分校的核心基础设施，这是规划预测药物开发AD转化中心所必需的。这将部分使用目前正在开发的基于网络的平台（系统医学阿尔茨海默氏症研究和治疗或SMART）来完成：//smart.ucsd.edu。资源的编目和整合，包括细胞和动物模型，试剂，化合物的化学库，处于不同开发阶段的现有化合物，生物样品，死后脑组织，方法，如高通量筛选和新生成的多组学数据集（包括来自细胞和动物模型的现有数据）的存档和注释，以及来自人类纵向研究的数据。一个主要的焦点将是利用来自非常好的表型患者（包括极端表型）的人iPSC（hiPSC）来尝试在培养皿模型中建立疾病。此外，我们将利用当地丰富的系统生物学，生物统计学和生物信息学生物工程，药理学，神经病理学和临床研究方面的专业知识，为研究生，医学实习生和博士后学者建立适当的QSP培训计划。最后，我们将确定实现高效数据共享的流程，并与制药公司建立强有力的合作关系。