The IU/JAX Alzheimer's Disease Precision Models Center: Aging

IU/JAX 阿尔茨海默病精密模型中心：衰老

基本信息

批准号：
9930786
负责人：
Gregory W Carter
金额：
$ 47.55万
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/9930786
关键词：
Academic Medical Centers Aging Alleles Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer’s disease biomarker Animal Disease Models Animal Model Animals 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 Genetic Models Genome engineering Genomic approach Genomics Goals Growth Heterogeneity Human Human Genetics Image Indiana Informatics Infrastructure 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 Resources Sampling Scientist Systems Biology Testing The Jackson Laboratory Therapeutic Translations United States United States National Institutes of Health Universities Variant amyloid precursor protein processing animal imaging causal variant cholesterol trafficking clinically relevant cost data resource disability disease phenotype drug testing effective therapy gene interaction genetic technology genome editing genome sequencing genome wide association study human disease imaging biomarker innovation insight mouse genome mouse model multidisciplinary neuroimaging neuroinflammation neuropathology next generation novel novel therapeutics pharmacokinetics and pharmacodynamics pre-clinical preclinical study prevent repository symposium synergism 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. !

项目摘要整体组件阿尔茨海默氏病（AD）是痴呆症，残疾和死亡的主要原因。尽管最近我们对广告潜在的基本生物学机制的理解的进步，我们尚不知道如何防止AD或具有经批准的疾病修饰干预措施。两者都必须减慢或停止增长至关重要在痴呆症患病率中。《国家阿尔茨海默氏症》项目法（NAPA）旨在预防和有效地对待广告到2025年，通过有关病因，早期检测和治疗的创新研究。支持纳帕的目标， NIA赞助的2015年阿尔茨海默氏病研究中确定的研究领域之一峰会是下一代AD动物模型的发展，这将证明具有更大的预测性临床前研究，因此加速了药物测试管道。而我们目前的广告动物模型有提供了多种对AD疾病机制的新颖见解，到目前为止尚未成功使用它们预测已进入AD临床试验的疗法的有效性。印第安纳大学（IU）/杰克逊实验室（JAX）阿尔茨海默氏病精密模型中心（IU/JAX ADPMC）将利用IU在神经退行性研究中的优势，包括25年的NIA支持阿尔茨海默氏病中心（ADC）和Jax的八个哺乳动物遗传学和疾病建模的数十年专业知识，以发展，验证和传播阿尔茨海默氏病（AD）的新的，精确的动物模型。此外，IU/JAX ADMPC包含Sage Bionetworks提供数据组织和传播方面的专业知识。 IU/JAX ADPMC带来一个国际多学科的团队 - 包括遗传学家和遗传技术专家，定量和计算生物学家，AD和神经影像学专家，药理学家和世界领导人正在发展精确的疾病模型 - 拥有集体在国际舞台上出现时，能够预见疾病建模的需求。这将允许 IU/JAX ADPMC有效，有效地为广告科学界服务。 IU/JAX ADPMC将生成新的广告建模过程和管道，数据资源，研究结果和模型将通过Jax和Sage的经过验证的传播管道以及NIA-将迅速分享支持广告中心，学术医疗中心，研究机构和制药行业全世界。最终，这将加速动物模型中进步的应用可能的医疗益处。 IU/JAX ADPMC的具体目的是： 1。最大化人类数据集，以识别AD的推定变体，基因和生物标志物。 2。生成并表征下一代AD的鼠标模型。 3。验证AD的下一代小鼠模型并开发临床前测试管道。呢