MITIGATION OF MULTI-ORGAN DELAYED EFFECTS OF ACUTE RADIATION EXPOSURE (DEARE) WITH ACE-INHIBITOR LISINOPRIL

使用 ACE 抑制剂赖诺普利缓解急性辐射暴露 (DEARE) 的多器官迟发效应

• 批准号: 10932591
• 负责人: JILL LANDRUM
• 金额: $ 110万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10932591
• 关键词: Acute; Adult; Angiotensin-Converting Enzyme Inhibitors; Animals; Childhood; Development; Documentation; Dose; Drug Kinetics; Ensure; Exposure to; FDA approved; Hematology; Human; Kidney Diseases; Licensure; Lisinopril; Organ; Pharmaceutical Preparations; Radiation Pneumonitis; Radiation Toxicity; Radiation exposure; Rattus; Safety; Survivors; Toxic effect; Whole-Body Irradiation; cohort; experience; irradiation; lead candidate; pre-clinical; radiation mitigation

Victims of acute radiation exposure are likely to experience a range of late multi-organ toxicities, which are collectively referred to as delayed effects of acute radiation exposure (DEARE). Currently there are no FDA-approved MCMs for DEARE. Lisinopril is a lead candidate MCM for mitigation of DEARE as it meets all the technical requirements for MCM development under this BAA including prior efficacy in animal studies and an established safety profile in humans. Our main objective is to build on our extensive preclinical experience to forward lisinopril through FDA-licensure as a countermeasure for DEARE. To meet this objective, we have developed the following three milestones. Milestone 1: Lisinopril dose optimization for mitigation of radiation pneumonitis. Milestone 2: Lisinopril efficacy in survivors of hematologic acute radiation syndrome (H-ARS). Milestone 3: Regulatory Activities.

急性辐射照射的受害者可能会出现一系列迟发性多器官毒性，统称为急性辐射照射的迟发性效应。目前，DEARE还没有FDA批准的MCM。赖诺普利是缓解DEARE的主要候选MCM，因为它符合本BAA下MCM开发的所有技术要求，包括动物研究中的既往疗效和已确立的人体安全性特征。我们的主要目标是建立在我们广泛的临床前经验，通过FDA许可证，作为DEARE的对策。为了实现这一目标，我们制定了以下三个里程碑。里程碑1：缓解放射性肺炎的赖诺普利剂量优化。里程碑2：赖诺普利在血液学急性放射综合征（H-ARS）幸存者中的疗效里程碑3：监管活动。