Preclinical Development of a GI Radiation Countermeasure

描述（由申请人提供）：人们意外或有目的地暴露于高水平辐射会造成严重的直接风险和潜在的长期健康风险。目前还没有FDA批准的放射性损伤后24- 48小时有效的抗辐射剂。因此，有一个关键的未满足的医疗需要，以保护人民免受这些有害影响的意外辐射。 我们确定，十八碳烯基硫代磷酸（OTP）在致死水平的？通过单次皮下注射的照射以1.2的剂量修正因子增加隐窝计数和存活。本申请的总体目标是将OTP开发为胃肠放射性激动剂，用于暴露于致命电离辐射的人类受试者，所述电离辐射是核事故或恐怖袭击的结果。 可交付成果将是“药物主文件”的非人灵长类动物安全性和有效性数据，以便根据FDA的动物规则提交研究性新药申请。 这项工作将在田纳西大学健康科学中心RxBio的生理学、药学和病理学系之间合作完成。Inc.和加州国家灵长类动物研究中心。该项目已准备好在获得资金后部署，并建立在研究团队以前的合作基础上。 大机会方案旨在“发展与公共卫生有关的创新”。用于治疗胃肠道急性辐射综合征的OTP的开发-本申请的主要目的-似乎对人类的利益具有重大的希望-因此，将对国家和世界产生重大影响。 公共卫生相关性声明：目前没有FDA批准的放射性损伤后24- 48小时有效的放射性药物。本项目将为十八烯基硫代磷酸盐作为胃肠道放射性激动剂用于暴露于致命电离辐射的人类受试者的“药物主文件”提供非人灵长类动物安全性和有效性数据，从而能够根据FDA动物规则提交IND申请。

DESCRIPTION (provided by applicant): Accidental or purposeful exposure of people to high levels of radiation poses a serious immediate risk and potential long-term health risk. NO FDA approved radiomitigant effective 24-48h after radiation injury is available today. Thus, there is a critical unmet medical need to shield the population from these harmful effects of unintended radiation. We established that octadecenyl thiophosphate (OTP) administered 26 h after lethal levels of ?-irradiation by a single subcutaneous injection increases crypt counts and survival with a dose modification factor of 1.2. The overall objective of this application is to develop OTP as a gastrointestinal radiomitigator for use in human subjects exposed to lethal ionizing radiation either as a result of nuclear accident or terrorist attack. The deliverable will be non-human primate safety and efficacy data for a "drug master file" enabling the filing of an Investigational New Drug application based on the Animal Rule of the FDA. This work will be completed in collaboration between the Departments of Physiology, Pharmaceutical Sciences, and Pathology of the University of Tennessee Health Science Center, RxBio. Inc. and the California National Primate Research Center. The project is ready to be deployed upon funding and builds on previous collaboration of the research team. The Grand Opportunities program aims the "development of innovations" linked to public health. Development of OTP for the treatment of the gastrointestinal acute radiation syndrome - the primary objective of the present application - appears to hold significant promise for the benefit of mankind - and as such, stands to significantly impact the country and the world. Public Health Relevance Statement: NO FDA approved radiomitigant effective 24-48h after radiation injury is available today. This project will provide non-human primate safety and efficacy data for a "drug master file" for octadecenyl thiophosphate as a gastrointestinal radiomitigator for use in human subjects exposed to lethal ionizing radiation enabling the filing of an IND application based on the Animal Rule of the FDA.