A novel Anti-endotoxin Peptide for Septic Shock

描述(由申请人提供)：一种用于感染性休克的新型抗内毒素多肽项目概述这项I期SBIR建议的目的是评估一种新型多肽CN16用于治疗感染性休克的可行性。目前对内毒素休克和感染性休克的治疗措施未能证明对脓毒症患者的有效治疗。最近，我们发现了一种名为CN16的多肽，具有很强的抗内毒素活性。由于CN16在阻断革兰氏阴性细菌脂多糖(LSP)的功能及其在感染性休克动物模型中的潜在益处方面非常有效，我们推测CN16将成为治疗感染性休克的有效候选药物。仅在美国，用于治疗感染性休克的候选药物的市场就达到170亿美元*(每个患者22,100美元)。全世界每年约有150万人患有败血症；美国每年新增70万例脓毒症确诊病例，死亡率为30%-50%*。由于老年患者数量的增加和免疫抑制疗法的使用，脓毒症的发病率预计在未来十年内将会增加。在这项I期研究中，我们的重点是通过两种脓毒症小鼠模型，在体外和体内验证CN16作为候选药物预防脂多糖介导的败血症休克。这些研究将有助于更好地理解CN16在革兰氏阴性细菌败血症/感染性休克的生物学中的作用。此外，这些研究的结果将构成SBIR第二阶段研究的基础，该研究将侧重于候选药物的临床前开发。我们的长期目标是开发一种治疗革兰氏阴性细菌败血症的抗内毒素治疗药物。潜在的治疗应用可能包括治疗腹膜炎、败血症和/或感染性休克患者。*Angus D等人。《急症护理医学》2001；29(7)：1303-1310。 公共卫生相关性：一种用于败血症休克的新型抗内毒素多肽项目描述我们正在提议一项治疗候选药物--抗内毒素多肽CN16用于治疗脓毒症的可行性研究。研究表明，CN16可以阻止一种重要的败血症介质与其靶点的相互作用，从而阻止一系列自我放大的炎症事件的启动，可能导致致命的后果。这项研究中获得的数据可能支持CN16作为临床候选药物的进一步发展。

DESCRIPTION (provided by applicant): A Novel Anti-Endotoxin Peptide for Septic Shock Project Summary The purpose of this Phase I SBIR proposal is to evaluate the feasibility of a novel peptide, CN16, for the treatment of septic shock. Current therapeutic interventions for endotoxin shock and septic shock fail to demonstrate effective treatment for patients with sepsis. Recently, we identified the peptide, CN16, for its potent anti-endotoxin activity. Because CN16 is so effective in blocking the function of gram-negative bacterial lipopolysaccharides (LSP) and its potential beneficial effects in animal models of septic shock, we hypothesize that CN16 will be an effective drug candidate for treating septic shock in patients. The market for a drug candidate for septic shock is $17 Billion* ($22,100/per patient) in the US alone. Approximately 1.5 M people world-wide suffer from sepsis annually; 700,000 new cases of sepsis annually are diagnosed in the U.S. with a 30-50% mortality rate*. The incidence of sepsis is expected to increase over the next decade due to increasing number of elderly patients and increased uses of immune suppressive therapies. Our focus for this Phase-I study is to validate CN16 as therapeutic candidate for the prevention of septic shock mediated by LPS in vitro and in vivo using two sepsis models in mice. These studies will lead to improved understanding of the role of CN16 in the biology to gram-negative bacterial sepsis/septic shock. In addition the results of these studies will form the basis for a SBIR phase-II study, which will focus on pre-clinical development of the drug candidate. Our long-range goal is to develop an anti-endotoxin therapeutic agent for gram-negative bacterial sepsis. The potential therapeutic applications may include treatment for patients with peritonitis, sepsis, and/or septic shock. *Angus D, et al. Crit Care Med 2001; 29(7): 1303-1310. PUBLIC HEALTH RELEVANCE: A Novel Anti-Endotoxin Peptide for Septic Shock Project Narrative We are proposing a feasibility study for a therapeutic drug candidate, the anti-endotoxin peptide CN16, for the treatment of sepsis. CN16 has been shown to prevent the interaction of an important sepsis mediator with its target and thus prevent the initiation of a self-amplifying cascade of inflammatory events with a possibly fatal outcome. The data obtained in this study may support further development of CN16 as a clinical development candidate.