Core E Animal Infection Models

Core E 动物感染模型

• 批准号: 10394989
• 负责人: David S Perlin
• 金额: $ 118.1万
• 依托单位: HACKENSACK UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394989
• 关键词: Acute; Aerosols; Animal Model; Animals; Bacteremia; Bacteria; Biological Assay; Biological Markers; Biotechnology; Chronic; Clinical; Communication; Cutaneous; Data; Development; Disease; Disease Marker; Disease model; ESKAPE pathogens; Ensure; Histopathology; Human Resources; Immune response; Infection; Inflammation; Lead; Lung; Lung infections; Mass Spectrum Analysis; Measurement; Methods; Modeling; Molecular; Morbidity - disease rate; Mucous Membrane; Multi-Drug Resistance; Multidrug-Resistant Tuberculosis; Multiple Bacterial Drug Resistance; Mus; Mycobacterium tuberculosis; Oral; Penetration; Pharmaceutical Preparations; Pneumonia; Reproducibility; Rodent; Route; Sepsis; Services; Site; Skin Tissue; Soft Tissue Infections; Spatial Distribution; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Systemic infection; Therapeutic; Thigh structure; Tissues; Treatment Efficacy; Tuberculosis; Work; Wound Infection; acute infection; analytical method; biodefense; chronic infection; design; drug development; drug resistant bacteria; drug resistant pathogen; experience; fluorescence imaging; in vivo; in vivo imaging; innovation; instrumentation; laser capture microdissection; liquid chromatography mass spectrometry; lung lesion; microbial; mortality; multi-drug resistant pathogen; new technology; next generation; novel; pathogen; pathogenic bacteria; pre-clinical; preclinical development; soft tissue; specific biomarkers; spectroscopic imaging; subcutaneous; treatment response

Abstract Assessing the treatment efficacy of novel leads against drug resistant bacteria in animal models is crucial for advancing compounds to the preclinical stage of development. Currently, there is a paucity of reproducible disease models with reliable metrics to assess lead compounds and even less facilities and personnel with the expertise to perform such important studies. To meet this important challenge, the Animal Model Core for this proposed CETR has developed reproducible systemic, pulmonary, soft tissue, wound, infection models in rodents for clinically important multidrug resistant bacteria. The Aims of the core are to: 1) provide small animal infection models for ESKAPE, TB and NTM pathogens to evaluate lead compounds, and 2) provide state of the art analytical services on host response and bacterial bio-burden distribution to assess and quantify lead compound treatment efficacy. The Animal core has functioned in this capacity for more than 15 years with experience supporting drug development for the academic, pharma and biotech sectors. Under the direction of Dr. David Perlin, it served as a multi-institutional regional animal core for the Region II RCE (Northeast Biodefense Center) for 11 years (2003-2013) and has supported the current CETR for the past 4+ years (2013 to present). The Animal Core operates at a very high capacity, having logged more than 1.8 million animal days of high threat bacterial agents since 2003. An experienced and dedicated animal model team performs a wide range of infection models with multiple routes of infections (iv, oral, aerosol, subcutaneous, mucosal) and markers for disease (morbidity/mortality, microbial burden, histopathology, etc.). The management staff of the Animal core works closely with both Project Leaders and other Core Directors to ensure that all novel leads are rapidly advanced through the development pipeline. This close and constant line of communication permits the necessary adjustments in design and execution of studies, and has resulted in the advancement of 7 promising leads in the Rutgers CETR projects from 2014 to 2018. the Animal core possesses cutting edge instrumentation for analysis of infections and therapeutic responses. The incorporation of reproducible animal models operated by highly experienced staff and utilizing novel technologies will advance and accelerate the development of promising Lead compounds against multidrug resistant bacteria. All services can be performed under high-level biocontainment with regulatory approval. !

摘要 在动物模型中评估新型电极导线对耐药细菌的治疗效果 对于将化合物推进到临床前开发阶段至关重要。目前，有一个 缺乏具有可靠指标的可重现疾病模型来评估先导化合物， 具有进行此类重要研究的专门知识的设施和人员较少。满足这一 这是一个重要的挑战，该提议的CETR的动物模型核心已经开发出可重复的 啮齿类动物的全身、肺部、软组织、伤口、感染模型，用于临床重要的 多重耐药细菌核心的目的是：1）提供小动物感染模型 ESKAPE、TB和NTM病原体评价先导化合物，以及2）提供最新技术水平 宿主反应和细菌生物负荷分布的分析服务，以评估和量化 先导化合物治疗效果。动物的核心已经在这个能力中运作了超过 拥有15年为学术、制药和生物技术领域提供药物开发支持的经验 板块在大卫柏林博士的指导下，它作为一个多机构的区域动物 核心区域II RCE（东北生物防御中心）11年（2003-2013），并已 在过去4年多的时间里（2013年至今），一直支持当前的CETR。动物核心运作 在一个非常高的能力，记录了超过180万动物日的高威胁细菌 自2003年以来的代理商。一个经验丰富和专门的动物模型团队进行了广泛的， 具有多种感染途径（静脉、口服、气雾剂、皮下、粘膜）的感染模型， 疾病标志物（发病率/死亡率、微生物负荷、组织病理学等）。的 动物核心的管理人员与项目负责人和其他核心人员密切合作， 董事确保所有新的线索通过开发渠道迅速推进。 这种紧密而恒定的通信线路允许在设计和 研究的执行，并导致在罗格斯大学的7个有前途的线索的进步 2014年至2018年的CETR项目。Animal Core拥有尖端器械， 分析感染和治疗反应。纳入可重复的动物模型 由经验丰富的工作人员操作，并利用新技术将推进和加速 开发有前景的抗多药耐药细菌的先导化合物。所有服务 可以在监管机构批准的高水平生物防护下进行。 !