The IU/JAX Alzheimer's Disease Precision Models Center

IU/JAX 阿尔茨海默病精密模型中心

基本信息

批准号：
9205077
负责人：
Gregory W Carter
金额：
$ 500万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9205077
关键词：
Academic Medical Centers Alleles Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease model Animal Disease Models Animal Model Area Behavior Biochemistry Biological Biological Markers Biological Process Biology Blood Vessels Cause of Death Cessation of life Clinic Clinical Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Communities Complex Computer Simulation Data Data Set Databases Dementia Development Disease Disease model Drug Industry Early Diagnosis Effectiveness Elderly Ensure Etiology Failure Functional disorder Funding Generations Genes Genetic Genome engineering Genomic approach Genomics Goals Growth Hereditary Disease Heterogeneity Human Human Genetics Image Indiana Informatics Institution International Intervention Laboratories Late Onset Alzheimer Disease Liquid substance Mammalian Genetics Medical Medicine Modeling Mus Nerve Degeneration Outcome Outcome Measure Pharmacology Phenotype Preclinical Testing Presenile Alzheimer Dementia Prevalence Process Psychology Research Research Infrastructure Resources Sampling Scientist Staging Systems Biology Testing The Jackson Laboratory Therapeutic Translations United States United States National Institutes of Health Universities Variant amyloid precursor protein processing animal data animal imaging cholesterol trafficking clinically relevant computer studies cost disability disease phenotype drug testing effective therapy gene interaction genetic technology genetic variant genome editing genome sequencing genome wide association study human disease imaging biomarker innovation insight meetings mouse genome mouse model neuroimaging neuroinflammation neuropathology next generation novel novel therapeutics pre-clinical preclinical study prevent repository symposium web portal

项目摘要

PROJECT SUMMARY OVERALL COMPONENT Alzheimer's disease (AD) is a major cause of dementia, disability and death in the elderly. Despite recent advances in our understanding of basic biological mechanisms underlying AD, we do not yet know how to prevent AD or have an approved disease modifying intervention. Both are essential to slow or stop the growth in dementia prevalence. The National Alzheimer's Project Act (NAPA) seeks to prevent and effectively treat AD by 2025 through innovative research on etiology, early detection, and therapeutics. In support of NAPA's goals, one of the targeted areas of research identified at the NIA sponsored 2015 Alzheimer's Disease Research Summit was the development of the next generation of animal models of AD that will prove more predictive in preclinical studies and thus accelerate the drug testing pipeline. While our current animal models of AD have provided multiple novel insights into AD disease mechanisms, thus far they have not been successfully utilized to predict the effectiveness of therapies that have moved into AD clinical trials. The Indiana University (IU)/Jackson Laboratory (JAX) Alzheimer's Disease Precision Models Center (IU/JAX ADPMC) will leverage IU's strengths in neurodegenerative research including 25 years as an NIA-supported Alzheimer's Disease Center (ADC) and considerable expertise in preclinical drug testing with JAX's eight decades of expertise in mammalian genetics and disease modeling to develop, validate and disseminate new, precise animal models of Alzheimer's disease (AD). In addition, the IU/JAX ADMPC contains Sage Bionetworks to provide expertise in data organization and dissemination. The IU/JAX ADPMC brings together an international, multi-disciplinary team—including geneticists and genetics technology experts, quantitative and computational biologists, clinical experts in AD and neuroimaging, pharmacologists and world leaders in the development of precision animal models of disease—that possesses the collective ability to foresee disease modeling needs as they emerge on the international stage. This will allow the IU/JAX ADPMC to serve the AD scientific community effectively and efficiently. The IU/JAX ADPMC will generate new AD modeling processes and pipelines, data resources, research results and models that will be swiftly shared through JAX's and Sage's proven dissemination pipelines and through the NIA- supported AD Centers, academic medical centers, research institutions and the pharmaceutical industry worldwide. Ultimately, this will accelerate the application of advances in animal models for the greatest possible medical benefit. The Specific Aims of the IU/JAX ADPMC are: 1. Maximize Human Datasets to Identify Putative Variants, Genes and Biomarkers for AD. 2. Generate and Characterize the Next Generation of Mouse Models of AD. 3. Validate the Next Generation of Mouse Models of AD and Develop a Preclinical Testing Pipeline. !

项目概要总体组成尽管近年来阿尔茨海默病（AD）是导致老年人痴呆、残疾和死亡的主要原因。尽管我们对 AD 基本生物学机制的理解取得了进展，但我们还不知道如何预防 AD 或采用经批准的疾病缓解干预措施对于减缓或阻止生长至关重要。国家阿尔茨海默病项目法案 (NAPA) 旨在预防和有效治疗 AD。到 2025 年，通过病因学、早期检测和治疗方面的创新研究来支持 NAPA 的目标。 NIA 赞助的 2015 年阿尔茨海默病研究确定的目标研究领域之一 Summit 是下一代 AD 动物模型的开发，该模型将在以下方面更具预测性：临床前研究，从而加速药物测试流程，而我们目前的 AD 动物模型已经完成。对 AD 疾病机制提供了多种新颖的见解，但迄今为止尚未成功利用预测已进入 AD 临床试验的疗法的有效性。 (IU)/杰克逊实验室 (JAX) 阿尔茨海默病精密模型中心 (IU/JAX ADPMC) 将利用 IU 在神经退行性研究方面的优势，包括作为 NIA 支持的 25 年阿尔茨海默病中心 (ADC) 以及 JAX 的 8 家临床前药物测试方面的丰富专业知识数十年在哺乳动物遗传学和疾病模型方面的专业知识，用于开发、验证和传播新型、精确的阿尔茨海默病 (AD) 动物模型此外，IU/JAX ADMPC 还含有 Sage。生物网络提供数据组织和传播方面的专业知识。一个国际化的多学科团队——包括遗传学家和遗传学技术专家，定量和计算生物学家、AD 和神经影像学临床专家、药理学家和开发精准疾病动物模型的世界领先者——拥有集体能够预见国际舞台上出现的疾病模型需求。 IU/JAX ADPMC 有效且高效地为 AD 科学界提供服务 IU/JAX ADPMC 将。生成新的 AD 建模流程和管道、数据资源、研究成果和模型将通过 JAX 和 Sage 经过验证的传播管道以及 NIA 迅速共享支持 AD 中心、学术医疗中心、研究机构和制药行业最终，这将加速动物模型进步的应用。 IU/JAX ADPMC 的具体目标是： 1. 最大限度地利用人类数据集来识别 AD 的假定变异体、基因和生物标志物。 2. 生成并表征下一代 AD 小鼠模型。 3. 验证下一代 AD 小鼠模型并开发临床前测试流程。！