Intercollaborative Radiation Countermeasure (INTERACT) Consortium for Advanced Development of Medical Countermeasures to Mitigate/Treat Acute and Delayed Radiation Syndromes

相互协作辐射对策 (INTERACT) 联盟，促进减轻/治疗急性和迟发性辐射综合症的医疗对策高级发展

• 批准号: 10194363
• 负责人: Isabel Lauren Jackson
• 金额: $ 266.97万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-16 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10194363
• 关键词: Acute; Adolescent; Adult; Advanced Development; Aging; Animal Model; Biological; Biological Markers; Biological Process; Blood; Cell Aging; Clinical; Clinical Trials; Communication; Cutaneous; Data; Development; Dose; Drug Kinetics; Elderly; Ensure; Event; Exposure to; Failure; Fostering; Funding; Funding Opportunities; Generations; Genomic Instability; Goals; Government Agencies; Hematopoietic; Hour; Inflammation; Injury; Investigation; Knowledge; Laboratory Research; Life; Maryland; Medical; Medical center; Miniature Swine; Mission; Mitochondria; Modeling; Molecular; Morbidity - disease rate; Multiple Organ Failure; National Institute of Allergy and Infectious Disease; Nuclear; Nuclear Accidents; Oryctolagus cuniculus; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pilot Projects; Population; Process; Quality of life; Radiation; Radiation Accidents; Radiation Injuries; Radiation Sicknesses; Radiation Syndromes; Radiation Toxicity; Radiation exposure; Radiology Specialty; Readiness; Recording of previous events; Recovery; Regulatory Pathway; Research Personnel; Resource Sharing; Resources; Safety; Services; Site; Technology Transfer; Testing; Therapeutic Intervention; Tissues; Treatment Efficacy; United States Food and Drug Administration; United States National Institutes of Health; Universities; Whole-Body Irradiation; animal rule; base; body system; data sharing; design; gastrointestinal; improved; industry partner; interdisciplinary approach; international partnership; medical countermeasure; medical schools; member; mortality; multidisciplinary; multiorgan injury; new therapeutic target; nonhuman primate; pharmacometrics; pre-clinical; programs; public health emergency; radiation countermeasure; research and development; synergism; tissue regeneration; Acute; Adolescent; Adult; Advanced Development; Aging; Animal Model; Biological; Biological Markers; Biological Process; Blood; Cell Aging; Clinical; Clinical Trials; Communication; Cutaneous; Data; Development; Dose; Drug Kinetics; Elderly; Ensure; Event; Exposure to; Failure; Fostering; Funding; Funding Opportunities; Generations; Genomic Instability; Goals; Government Agencies; Hematopoietic; Hour; Inflammation; Injury; Investigation; Knowledge; Laboratory Research; Life; Maryland; Medical; Medical center; Miniature Swine; Mission; Mitochondria; Modeling; Molecular; Morbidity - disease rate; Multiple Organ Failure; National Institute of Allergy and Infectious Disease; Nuclear; Nuclear Accidents; Oryctolagus cuniculus; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pilot Projects; Population; Process; Quality of life; Radiation; Radiation Accidents; Radiation Injuries; Radiation Sicknesses; Radiation Syndromes; Radiation Toxicity; Radiation exposure; Radiology Specialty; Readiness; Recording of previous events; Recovery; Regulatory Pathway; Research Personnel; Resource Sharing; Resources; Safety; Services; Site; Technology Transfer; Testing; Therapeutic Intervention; Tissues; Treatment Efficacy; United States Food and Drug Administration; United States National Institutes of Health; Universities; Whole-Body Irradiation; animal rule; base; body system; data sharing; design; gastrointestinal; improved; industry partner; interdisciplinary approach; international partnership; medical countermeasure; medical schools; member; mortality; multidisciplinary; multiorgan injury; new therapeutic target; nonhuman primate; pharmacometrics; pre-clinical; programs; public health emergency; radiation countermeasure; research and development; synergism; tissue regeneration

PROJECT SUMMARY/ABSTRACT - OVERALL The Inter-collaborative Radiation Countermeasures (INTERACT) Consortium was assembled for the overall goal of developing safe and effective medical countermeasures (MCM) to mitigate and/or treat the acute, delayed, and long-term consequences of radiation exposure for all subsets of the civilian population in the event of a radiological or nuclear (RadNuc) public health emergency. The biological complexity of multiorgan injury (MOI) and failure associated with acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE) requires a comprehensive, multidisciplinary approach to efficiently identify new targets for therapeutic intervention and to move promising MCMs from the research laboratory to advanced pharmaceutical development and approval under the U.S. Food and Drug Administration’s (FDA) Animal Rule (AR) regulatory pathway. INTERACT, a newly formed University of Maryland School of Medicine (UMSOM)-based Center for Medical Countermeasures against Radiation (CMCR), is a partnership of internationally-recognized investigators from four U.S.-based universities who possess a broad depth of expertise in MCM development, a unique set of animal model platforms, and a common goal of sharing ideas and quality practices to advance the cutting-edge scientific discovery and translational development of MCMs. INTERACT projects are broadly designed around a common theme to promote tissue regeneration through targeting the biological processes involved in cellular degeneration that contribute to the clinical manifestation of ARS/DEARE after prompt exposure to high-doses of total body irradiation (TBI). Candidate MCMs under investigation target key biological mechanisms associated with a radiation-induced accelerated aging process including genomic instability, mitochondrial damage, cellular senescence, and inflammation that leads to the hematopoietic (Project 1) and gastrointestinal subsyndromes of ARS (Projects 2, 3), cutaneous radiation injury (Project 3), and DEARE (Projects 1 and 4). Preliminary datum for each of the MCMs under investigation in Projects 1-4 have shown a significant improvement in survival when administered at least 24 hours post- exposure and strong safety profiles in preclinical, and in some cases clinical trials. To advance MCM development within the framework of the AR regulatory pathway for all subsets of the population, projects are supported by two service cores (Core A- Administrative, Core B- Multispecies Efficacy and Pharmacometric Modeling Core) and two consortium cores (Coordinating Center Core, and the Opportunities Fund Management Core). Core B offers one of, if not the most, comprehensive animal model platforms available for MCM testing within the broader CMCR consortia, and includes rabbit, minipig, and non-human primate models of ARS and/or DEARE. INTERACT is synergistic with other potential Centers by offering capabilities and resources currently unavailable to other sites through data and resource sharing and technology transfer to advance and strengthen the National Institute of Allergy and Infectious Diseases (NIAID)/National Institute of Health (NIH)’s mission to ensure the nation’s preparedness to respond to a radiological or nuclear incident.

项目摘要/摘要 - 总体 整体组装了合并间的辐射对策（Intervort）联盟 开发安全有效的医疗对策（MCM）以减轻和/或治疗急性， 在这种情况下，延迟的辐射暴露对平民的所有子集的延迟和长期后果 放射线或核（RADNUC）公共卫生紧急情况。多器官损伤的生物复杂性 （MOI）和与急性辐射病（ARS）和急性辐射暴露的延迟作用相关的失败 （亲爱的）需要一种全面的多学科方法来有效地识别治疗的新目标 干预并将承诺MCM从研究实验室转移到先进的药物 根据美国食品和药物管理局（FDA）动物规则（AR）监管的开发和批准 路径。互动，新成立的马里兰大学医学院（UMSOM）的中心 针对辐射的医学对策（CMCR）是国际认可的研究人员的合作伙伴关系 来自四所美国大学的大学，他们在MCM开发方面拥有广泛的专业知识，这是一组独特的 动物模型平台，以及共享思想和质量实践以推动前沿的共同目标 MCMS的科学发现和翻译发展。 互动项目是围绕一个共同主题设计的，以促进组织再生 针对涉及细胞变性的生物学过程，这有助于 迅速暴露于大量全身照射（TBI）后，ARS/DEARE。候选人MCMS 投资目标关键生物学机制与辐射引起的加速老化过程相关 包括基因组不稳定性，线粒体损伤，细胞感应和注射，导致 ARS的造血（项目1）和胃肠道次核（项目2，3），皮肤辐射损伤 （项目3）和Deare（项目1和4）。每个正在调查的MCM的初步基准 项目1-4在至少24小时后给药时显示出生存率的显着提高 - 临床前的暴露和强大安全性，在某些情况下进行临床试验。推进MCM 在所有人口所有子集的AR监管途径框架内的发展，项目是 由两个服务核心（核心A-行政，核心B-多物种功效和药物计量学）支持 建模核心）和两个联盟核心（协调中心核心以及机会基金 管理核心）。核心B提供可用于的，即使不是最全面的动物模型平台之一 MCM在更广泛的CMCR财团内进行了测试，包括兔子，Minipig和非人类灵长类动物模型 Ars和/或Deare。 通过提供目前提供功能和资源，互动与其他潜在中心具有协同作用 通过数据，资源共享和技术转移无法获得其他网站，以提高和实力 美国国家过敏和传染病研究所（NIAID）/国家卫生研究院（NIH）的使命 确保国家准备对放射线或核事件做出反应。