PRECLINICAL DEVELOPMENT OF A GI RADIATION COUNTERMEASURE

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 in murine models that octadecenyl thiophosphate (OTP) administered 26 h after lethal levels of gamma-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. 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.