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. !

抽象的 在动物模型中评估新先导药物对抗耐药细菌的治疗效果 对于将化合物推进临床前开发阶段至关重要。目前，有一个 缺乏可重复的疾病模型和可靠的指标来评估先导化合物，甚至 具有进行此类重要研究所需专业知识的设施和人员较少。为了满足这个 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、感染模型对于临床具有重要意义 多重耐药细菌。核心目标是：1）提供小动物感染模型 针对 ESKAPE、TB 和 NTM 病原体评估先导化合物，以及 2) 提供最先进的技术 关于宿主反应和细菌生物负荷分布的分析服务，以进行评估和量化 先导化合物的治疗效果。动物核心以这种能力发挥作用已经超过了 拥有 15 年支持学术、制药和生物技术药物开发的经验 部门。在 David Perlin 博士的指导下，它作为一个多机构的区域动物 11 年来（2003 年至 2013 年）一直是第二区 RCE（东北生物防御中心）的核心 在过去 4 年多的时间里（2013 年至今）支持当前的 CETR。动物核心运作 以非常高的容量记录了超过 180 万个动物日的高威胁细菌 自 2003 年起成为代理商。经验丰富且专注的动物模型团队执行广泛的 具有多种感染途径（静脉注射、口腔、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）。这 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 董事确保所有新颖的线索都能通过开发渠道快速推进。 这种密切而持续的沟通渠道允许对设计和设计进行必要的调整。 执行研究，并在罗格斯大学取得了 7 个有前景的线索的进展 2014 年至 2018 年的 CETR 项目。动物核心拥有尖端仪器，可用于 分析感染和治疗反应。纳入可重复的动物模型 由经验丰富的员工操作并利用新技术将推动并加速 开发有前景的针对多重耐药细菌的先导化合物。所有服务 经监管部门批准，可以在高级生物防护下进行。 ！