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: 10401455
• 负责人: France Carrier
• 金额: $ 243.81万
• 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/10401455
• 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

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.

项目概要/摘要 - 总体 相互协作辐射对策（INTERACT）联盟的成立是为了整体 制定安全有效的医疗对策（MCM）以减轻和/或治疗急性、 辐射暴露对事件中所有平民群体造成的延迟和长期后果 放射或核 (RadNuc) 公共卫生紧急事件的多器官损伤的生物复杂性。 (MOI) 和与急性放射病 (ARS) 相关的失败以及急性辐射暴露的延迟效应 （DEARE）需要一种全面的、多学科的方法来有效地确定治疗的新靶点 干预并将有前途的 MCM 从研究实验室转移到先进的制药领域 根据美国食品和药物管理局 (FDA) 动物规则 (AR) 监管进行开发和批准 INTERACT 是一个新成立的马里兰大学医学院 (UMSOM) 中心。 辐射医学对策 (CMCR) 是国际公认的研究人员的合作伙伴关系 来自四所美国大学，这些大学在 MCM 开发方面拥有广泛而深入的专业知识，拥有一套独特的 动物模型平台，以及分享想法和质量实践以推进尖端技术的共同目标 MCM 的科学发现和转化发展。 INTERACT 项目广泛围绕一个共同主题设计，通过以下方式促进组织再生 针对参与细胞变性的生物过程，这些过程有助于临床表现 ARS/DEARE 立即暴露于高剂量全身照射 (TBI) 下的候选 MCM 后。 研究目标是与辐射引起的加速衰老过程相关的关键生物学机制 包括基因组不稳定、线粒体损伤、细胞衰老和炎症，这些都会导致 ARS 的造血（项目 1）和胃肠道亚综合征（项目 2、3）、皮肤放射损伤 （项目 3）和 DEARE（项目 1 和 4）。 项目 1-4 在治疗后至少 24 小时进行时显示出存活率的显着改善。 临床前和某些情况下的临床试验中的暴露和强大的安全性以推进 MCM。 在针对所有人群的 AR 监管途径框架内进行开发，项目是 由两个服务核心支持（核心 A- 管理、核心 B- 多物种功效和药理学 建模核心）和两个联合体核心（协调中心核心和机会基金） 管理核心）核心 B 提供了一种（如果不是最全面的）动物模型平台。 在更广泛的 CMCR 联盟内进行 MCM 测试，包括兔子、小型猪和非人类灵长类动物模型 ARS 和/或 DEARE。 INTERACT 通过提供当前的能力和资源与其他潜在中心产生协同作用 通过数据和资源共享以及技术转让来推进和加强其他站点无法获得的 美国国家过敏和传染病研究所 (NIAID)/美国国家卫生研究院 (NIH) 的使命 确保国家做好应对放射性或核事件的准备。