Core C: Animal and Imaging Core

核心 C：动物和成像核心

基本信息

批准号：
9766944
负责人：
Kewal Asosingh
金额：
$ 30.74万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9766944
关键词：
Acute Agonist Air Allergens Animal Experiments Animal Model Animals Area Aspergillus Asthma Biological Models Bronchodilator Agents Chronic Clinic Collaborations Complex Data Databases Densitometry Diet Dose Drug Formulations Drug Industry Drug Kinetics Ensure Equipment Experimental Models Frequencies Functional disorder Generations High Fat Diet Histologic Homeostasis Human IACUC Image Immune In Vitro Inflammation Interleukin-17 Intraperitoneal Injections Label Laboratory mice Link Logistics Lung Maintenance Management Information Systems Measurement Metabolic Metabolism Modeling Mus Nebulizer Oral Ovalbumin Paraffin Embedding Pathway interactions Performance Pharmaceutical Preparations Pre-Clinical Model Procedures Process Pyroglyphidae Radiation Research Route Safety Sampling Secure Services Side Signal Pathway Specimen Techniques Testing Therapeutic Therapeutic Effect Tissues Velocimetries X-Ray Tomography adaptive immune response airway hyperresponsiveness airway inflammation airway remodeling animal imaging asthma model asthmatic patient biobank cloud based cost data management drug testing eosinophilic asthma experimental study innovation insight instrument intravenous injection mouse model peptidomimetics pre-clinical preclinical study programs small molecular inhibitor success therapeutic evaluation tissue processing

项目摘要

ABSTRACT – CORE C The Animal and Imaging Core will support Projects of the Program by providing logistic and scientific oversight, and performance of complex longitudinal animal experiments. Various murine asthma models representing different human asthma endotypes across the TH2-TH17 immune spectrum, including ovalbumin allergen, house dust mite, Aspergillus, high fat diet, and a combination of high fat diet plus house dust mite will be made available to projects to test the therapeutic effects of IL-17A pathway inhibition using peptidomimetics and sGC stimulators/activators on airway hyper-reactivity and inflammation. Pharmacokinetics studies of compounds will be performed to determine optimal route, dose and frequency of administration. Intranasal, oral gavage, intravenous and intraperitoneal injection, and nebulized administration are available. Measurements of airway hyper-reactivity, 4Dx airflow, tracheal densitometry, airway inflammation and airway remodeling will be performed to analyze drug effects. 4Dx Imaging is a cutting edge X-ray tomographic velocimetric quantification of regional airflow allowing us to identify specific part(s) of the lungs targeted by the new compounds. A cloud- based mouse laboratory information management system (mLIMS) will be used to record all experimental procedures and to securely store all mouse data. All required instruments and expertise are found in the Core or made available through collaboration, such as equipment for 4Dx imaging and pharmaceutical industry guidance for drug formulation for the various routes of administration. The Core expedites results and reduces cost of Projects through the use of shared model systems and, most importantly, assists in the generation of preclinical data to move new, more effective, therapeutics into the clinic. New model systems of endotypes of asthma, preclinical studies and airflow imaging increase overall translational innovation of the Program.

摘要 - 核心C 动物和成像核心将通过提供后勤和科学监督来支持该计划的项目和复杂的纵向动物实验的性能。代表各种鼠哮喘模型跨Th2-Th17免疫光谱的不同人类哮喘内型，包括卵蛋白过敏原，将制作家庭尘螨，曲霉，高脂饮食以及高脂饮食加上家用尘螨的组合可用于测试使用Pepperomimetics和SGC抑制IL-17A途径的治疗作用的项目气道高反应性和炎症的刺激器/激活剂。化合物的药代动力学研究将进行以确定最佳途径，剂量和给药频率。鼻内，口腔吹牛，静脉注射和腹膜内注射以及雾化的给药可用。气道的测量过度反应性，4DX气流，气管密度法，气道注入和气道重塑进行分析药物作用。 4DX成像是尖端X射线层析成像式量化定量区域气流使我们能够确定新化合物靶向的肺的特定部分。云 - 基于鼠标的实验室信息管理系统（MLIM）将用于记录所有实验程序并安全存储所有鼠标数据。所有必需的工具和专业知识都在核心中找到或通过协作提供的，例如4DX成像和制药行业的设备针对各种管理途径的药物制定指南。核心加快结果并减少通过使用共享模型系统的成本，最重要的是，有助于生成临床前数据将新的，更有效的疗法转移到诊所。内型的新模型系统哮喘，临床前研究和气流成像增加了该程序的总体翻译创新。