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Pre-Clinical Testing Core

临床前测试核心

基本信息

批准号：
10006152
负责人：
Paul Richard Territo
金额：
$ 143.02万
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/10006152
关键词：
Age Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease pathology Animal Model Back Behavioral Biochemical Bioinformatics Biological Biological Assay Biological Markers Biological Models Biological Process Clinical Clinical Pharmacology Clinical Trials Communities Complex Core Facility Data Databases Development Disease Disease model Drug Kinetics Drug usage Evaluation Face Failure Future Generations Genomic approach Image Indiana Intellectual Property Laboratories Laboratory mice Levetiracetam Liquid substance Logistics Methodology Modeling Mus Neuropharmacology Pathologic Phenotype Physiological Physiology Pre-Clinical Model Preclinical Testing Protocols documentation Reporting Reproducibility Research Research Personnel Resources Rodent Model Schedule Standardization Symptoms System Testing The Jackson Laboratory Therapeutic Therapeutic Agents Therapeutic Effect Transgenic Organisms Translating Triage Universities Validation age related animal imaging assay development beta-site APP cleaving enzyme 1 clinical translation clinically relevant data warehouse design digital drug discovery efficacy study experimental study gamma secretase genome editing in vivo in vivo imaging inhibitor/antagonist insight interest method development mouse genetics mouse model neurobehavioral neuroimaging novel novel therapeutics pharmacodynamic biomarker pharmacokinetics and pharmacodynamics preclinical efficacy preclinical evaluation preclinical imaging prevent protocol development repository screening skills tool training opportunity

项目摘要

PROJECT SUMMARY PRECLINICAL TESTING CORE (PTC) The Preclinical Testing Core (PTC) of the IU/JAX Alzheimer’s Disease Precision Models Center will establish and validate a preclinical testing screening strategy pipeline with predetermined go/no-go decision points using pharmacokinetics, pharmacodynamic biomarkers and functional assessments in biologically and pathologically relevant AD mouse models that allow standardized and unbiased assessments of potential therapeutic agents. The Core is led by experts in preclinical imaging, neuropharmacology, and animal model characterization at IU’s Center for Neuroimaging and JAX’s Mouse Neurobehavioral Phenotyping, In Vivo Imaging, and Physiology Core facilities, and supported by IU’s Clinical Pharmacology Analytical Core. The pipeline’s primary and secondary screens focus on generating pharmacokinetic (PK) and pharmacodynamic (PD) biomarker assessments in two new generation AD mouse models with construct validity. Only test compounds that demonstrate target engagement in the biomarker screens will move to tertiary screening for in vivo symptom modifying effects and determination of the novel compound’s therapeutic window. The specific aims of the PTC are (1) the establishment of a standardized testing pipeline, the development of the assay protocols and methods, the creation of the data repository and back-translating clinical compound failures; (2) validating the pipeline with two compounds currently in clinical trials in two biologically and pathologically relevant animal models; (3) the evaluation of novel test compounds through the pipeline which allows investigators in the greater AD research community with unprecedented access to a validated pipeline, standardized testing protocols, and resources to screen compounds of interest.

项目摘要临床前试验核心(PTC) IU/JAX阿尔茨海默病精确模型中心临床前测试核心(PTC)将建立以及验证具有预定通过/不通过决策点的临床前测试筛选策略流水线生物病理学中的药代动力学、药效生物标志物和功能评价相关的AD小鼠模型，允许对潜在的治疗剂进行标准化和公正的评估。 Core由临床前成像、神经药理学和动物模型表征方面的专家领导，网址为印第安纳大学神经成像中心和JAX的小鼠神经行为表型，活体成像，以及生理学核心设施，并得到印第安纳大学临床药理分析核心的支持。这条管道的主要二次筛查侧重于产生药代动力学(PK)和药效学(PD)生物标志物两种新一代AD小鼠模型的结构效度评估。仅测试符合以下条件的化合物展示生物标记物筛查的目标参与度将转移到体内症状的第三级筛查新化合物的修饰作用及治疗窗的确定。《公约》的具体目标 PTC是(1)建立标准化的检测管道，制定检测方案和方法：建立数据库，回译临床用药失败；(2)验证目前正在对两种生物和病理相关动物进行临床试验的两种化合物的管道模型；(3)通过管道对新的测试化合物进行评估，使研究人员能够在更大的AD研究社区，史无前例地访问经过验证的管道、标准化测试协议和资源来筛选感兴趣的化合物。