Core E Animal Infection Models

Core E 动物感染模型

• 批准号: 10613892
• 负责人: David S Perlin
• 金额: $ 144.96万
• 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/10613892
• 关键词: Acceleration; Acute; Aerosols; Animal Model; Animals; Bacteremia; Bacteria; Biological Assay; Biological Markers; Biotechnology; Chronic; Clinical; Communication; Cutaneous; Data; Dedications; Development; Disease; Disease Marker; Disease model; ESKAPE pathogens; Histopathology; Human Resources; Immune response; Infection; Inflammation; Institution; 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; 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; non-tuberculous mycobacterial infection; novel; pathogen; pathogenic bacteria; pre-clinical; preclinical development; soft tissue; specific biomarkers; spectroscopic imaging; subcutaneous; treatment response; wound

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 用动物模型评价新型先导化合物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 缺乏可复制的疾病模型，缺乏可靠的指标来评估先导化合物，甚至 更少的设施和具有专业知识的人员来进行如此重要的研究。为了满足这一点 重大挑战，拟议的CETR的动物模型核心已开发出可重复性 啮齿动物全身、肺、软组织、创伤、感染模型的临床意义 耐多药细菌。该中心的目标是：1)提供小动物感染模型 为ESKAPE、TB和NTM病原体评估先导化合物，以及2)提供最新技术 对宿主反应和细菌生物负荷分布的分析服务，以评估和量化 含铅化合物的治疗效果。动物核心已经在这方面发挥了作用超过 15年在学术、制药和生物技术领域支持药物开发的经验 扇区。在大卫·佩林博士的指导下，它成为了一个多机构的地区性动物 为第二区域RCE(东北生物防御中心)工作了11年(2003-2013)，并 在过去4年多的时间里(2013年至今)支持目前的《经济、社会和文化权利国际公约》。动物核心运作 在非常高的产能下，已经记录了180多万个动物日的高威胁细菌 自2003年起代理。一支经验丰富且敬业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)和 疾病标记物(发病率/死亡率、微生物负担、组织病理学等)。这个 动物核心的管理人员与项目负责人和其他核心密切合作 董事，以确保所有新的线索在开发管道中迅速推进。 这条紧密而持续的沟通渠道允许在设计和设计方面进行必要的调整 进行研究，并在罗格斯大学取得了7项有希望的领先优势 经济、社会和文化权利国际组织2014年至2018年的项目。动物核心拥有尖端的仪器设备 感染和治疗反应的分析。纳入可复制的动物模型 由经验丰富的员工运营，并利用新技术将推动和加速 抗多重耐药细菌的有前景的先导化合物的开发。所有服务 可以在监管批准的高水平生物遏制下进行。 好了！