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肽项目概述本I期SBIR提案的目的是评估新型肽CN 16用于治疗感染性休克的可行性。目前内毒素休克和感染性休克的治疗干预未能证明对脓毒症患者的有效治疗。最近，我们鉴定了肽CN 16，其有效的抗内毒素活性。由于CN 16在阻断革兰氏阴性细菌脂多糖（LSP）的功能方面如此有效，并且其在感染性休克动物模型中的潜在有益作用，我们假设CN 16将是治疗感染性休克患者的有效候选药物。仅在美国，败血性休克候选药物的市场价值就达170亿美元 *（每例患者22，100美元）。全世界每年约有150万人患有败血症;在美国每年诊断出70万例败血症新病例，死亡率为30-50%*。由于老年患者数量的增加和免疫抑制治疗的使用增加，预计脓毒症的发病率在未来十年将增加。我们的第一阶段研究的重点是验证CN 16作为治疗候选预防感染性休克介导的LPS在体外和体内使用两个脓毒症模型在小鼠。这些研究将有助于更好地了解CN 16在革兰氏阴性细菌脓毒症/脓毒性休克生物学中的作用。此外，这些研究的结果将构成SBIR II期研究的基础，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抗内毒素治疗革兰氏阴性细菌脓毒症的药物。潜在的治疗应用可能包括腹膜炎、脓毒症和/或脓毒性休克患者的治疗。* 安格斯D等人，《危重病护理医学》2001; 29（7）：1303-1310。 公共卫生相关性：一种新的抗内毒素肽治疗脓毒症休克项目叙述我们正在提出一个可行性研究的治疗药物候选人，抗内毒素肽CN 16，用于治疗脓毒症。CN 16已被证明可以防止一种重要的脓毒症介质与其靶点的相互作用，从而防止引发具有可能致命结果的炎症事件的自放大级联反应。本研究中获得的数据可支持CN 16作为临床开发候选药物的进一步开发。

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.