Development of RLIP76 protein as a Radiation Countermeasure

描述（由申请人提供）： 仍然迫切需要能够抵消辐射照射毒性影响的药物。Terapio正在开发一种重组蛋白RLIP 76，用作工人、军事人员或平民的辐射防护剂，这些人要么面临辐射暴露的紧迫危险， 或者已经被感染了在德克萨斯大学阿灵顿分校进行的研究中，发现脂质体中递送的RLIP 76在保护暴露于致命剂量辐射的小鼠方面具有显著效果，即使蛋白脂质体在暴露后24小时施用。Terapio的成立是为了开发和商业化这种蛋白质，用作辐射防护剂。该公司获得了I期SBIR，其中进行了探索性疗效研究，证实了RLIP 76蛋白脂质体通过各种给药途径（包括皮下和肌内注射）的显著疗效，这对于必须在现场提供的治疗具有显著优势。现在，该公司正在申请第二阶段SBIR，以继续这项工作，并进行必要的研究，以提交IND。具体来说，目前申请的目标是：1。）为IND启动研究开发必要的检测方法，并在FDA要求的程度上验证拟议的组织水平作用机制; 2.）进行IND赋能研究; 3.）按照FDA的要求，在两个物种（大鼠和灵长类动物）中进行动物安全性和毒代动力学研究。成功完成这些目标将使公司能够提交IND，为进行关键动物疗效和人体安全性研究做准备，以支持后续的新药申请。

DESCRIPTION (provided by applicant): There remains a critical need for medicines that can counteract the toxic effects of radiation exposure. Terapio is developing a recombinant protein, RLIP76, for use as a radioprotectant for workers, military personnel, or civilians that are either in imminent danger of radiation exposure, or have already been exposed. In research carried out at the University of Texas at Arlington, RLIP76 delivered in a liposome was discovered to have significant effects in protecting mice exposed to otherwise lethal doses of radiation, even if the proteoliposome was administered as late as 24 hours after exposure. Terapio was formed to develop and commercialize the protein for use as a radioprotectant. The company was awarded a Phase I SBIR from which exploratory efficacy studies were carried out confirming significant efficacy of the RLIP76 proteoliposome by a variety of routes of administration, including subcutaneous and intramuscular injection, a marked advantage for therapy that has to be delivered in the field. Now the company is applying for a Phase II SBIR to continue that work and carry out the studies necessary to file for an IND. Specifically, the goals of the current application are: 1.) to develop the necessary assays for IND-enabling studies and to verify the proposed tissue-level mechanism of action to the degree required by the FDA; 2.) to perform IND-enabling studies and 3.) to carry out animal safety and toxicokinetic studies in two species (rat and primate) as required by the FDA. Successful completion of these goals will position the company to file an IND in preparation for performing pivotal animal efficacy and human safety studies to support a subsequent New Drug Application.