Neuroprotective Apolipoprotein-E Analogs Continuation

描述(申请人提供)：在我们之前的资助中，我们开发了COG1410，一种具有额外神经保护特性的新型抗炎肽，用于治疗创伤性脑损伤(TBI)。每年，美国有50,000人死于创伤性脑损伤，在接受治疗并从紧急卫生设施出院的100万美国人中，有230,000名幸存者残疾，以至于他们的余生需要大量的护理。在开放性和闭合性颅脑损伤动物模型中，伤后2小时给予COG1410。与对照组相比，接受COG1410治疗的动物在平衡、协调、运动控制、学习和记忆测试中的后续表现显著改善。基于在动物身上的成功，我们的临床目标是对脑外伤患者进行药物干预，减轻脑损伤反应的严重性，从而改善结果，如能够在没有外部帮助的情况下进行正常和独立的日常生活活动。这项申请是为了执行食品和药物管理局(FDA)为提交和批准COG1410的研究新药(IND)申请所需的所有安全性和毒性研究。综上所述，我们需要合成高质量的COG1410，并使用良好实验室操作规范(GLP)方法来分析不同基质中的COG1410，通过静脉注射不同剂量的COG1410来测量大鼠和狗的药代动力学(PK)和毒代动力学(TK)，并评估COG1410在大鼠和狗身上的安全性。对IND所需的其他研究也进行了详细说明。这项申请的总体目标是成功完成启动COG1410在人体上的第一阶段临床试验所需的所有研究、监管报告提交和必要的批准。公共卫生相关性：我们开发了COG1410，一种具有额外神经保护特性的新型抗炎肽，用于治疗创伤性脑损伤(TBI)。每年，美国有50,000人死于创伤性脑损伤，在接受治疗并从紧急卫生设施出院的100万美国人中，有230,000名幸存者残疾，以至于他们的余生需要大量的护理。目前，还没有FDA批准的创伤性脑损伤的治疗方法，这一申请的重点是将COG1410这一确实保护动物免受脑损伤的研究新药带入人类临床试验和人类脑损伤患者。

DESCRIPTION (provided by applicant): In our previous grants, we have developed COG1410, a novel anti-inflammatory peptide with additional neuroprotective properties, for the treatment of Traumatic Brain Injury (TBI). Each year, TBI accounts for 50,000 deaths in the United States and of the 1,000,000 Americans treated and released from the Emergency Health Facilities, 230,000 survivors are disabled to the point that they will require significant care for the rest of their lives. In animal models of open and closed TBI, COG1410 was given 2 hours following the injury. Subsequent performance of COG1410 treated animals was significantly improved compared to controls on tests of balance, coordination, motor control, learning and memory. Based on the success in animals, our clinical goal is to intervene with a drug therapy in TBI patients that would lessen the severity of the response to TBI and thereby improve outcomes, like being capable of normal and independent activities of daily living without external assistance. This application is to perform all of the safety and toxicity studies required by the Food and Drug Administration (FDA) for submission and approval of an Investigational New Drug (IND) application for COG1410. In overview, we are required to synthesize high-quality COG1410 and use Good Laboratory Practices (GLP) methods to analyze COG1410 in different matrices, measure pharmacokinetics (PK) and toxicokinetics (TK) in rats and dogs using different amounts of COG1410 via intravenous injection and assess the safety of COG1410 in rats and dogs. Additional studies required of the IND are also detailed. The overall goal of this application is the successful completion of all studies, regulatory report submissions and necessary approvals that are needed to begin Phase 1 clinical trials of COG1410 in humans. PUBLIC HEALTH RELEVANCE: We have developed COG1410, a novel anti-inflammatory peptide with additional neuroprotective properties, for the treatment of Traumatic Brain Injury (TBI). Each year, TBI accounts for 50,000 deaths in the United States and of the 1,000,000 Americans treated and released from the Emergency Health Facilities, 230,000 survivors are disabled to the point that they will require significant care for the rest of their lives. Currently, there are no FDA approved treatments for Traumatic Brain Injury and the focus of this application is to bring COG1410, an investigational new drug that does protect animals from TBI, to human clinical trials and to human TBI patients.