Preclinical Development of a GI Radiation Countermeasure

描述(由申请人提供)：人们意外或故意暴露在高水平的辐射中会构成严重的直接风险和潜在的长期健康风险。今天没有FDA批准的在辐射损伤后24-48小时有效的放射增强剂。因此，有一个关键的未得到满足的医疗需求，即保护人们免受这些意外辐射的有害影响。 我们发现，在致死剂量照射后26小时，单次皮下注射十八碳烯基硫代磷酸(OTP)可增加隐窝数量和存活率，剂量修正系数为1.2。这一应用的总体目标是开发OTP作为胃肠道放射增强剂，用于因核事故或恐怖袭击而暴露于致命电离辐射的人体受试者。 可交付的数据将是非人类灵长类动物的安全性和有效性数据，以便根据FDA的动物规则提交研究新药申请。 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。公司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，并建立在研究小组以前合作的基础上。 “大机遇”计划旨在“发展与公共健康相关的创新”。开发用于治疗胃肠道急性辐射综合征的OTP--本申请的主要目标--似乎为造福人类带来了巨大的希望，因此，将对国家和世界产生重大影响。 公共卫生相关声明：今天没有FDA批准的放射增强剂在辐射损伤后24-48小时有效。该项目将提供非人类灵长类动物的安全性和有效性数据，用于将十八烯基硫代磷酸作为胃肠道放射增强剂，用于暴露在致命性电离辐射下的人体受试者，使其能够根据FDA的动物规则提交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.