Development of New Agent to Treat Toxin Induced Sepsis

开发治疗毒素引起的败血症的新药

• 批准号: 6584499
• 负责人: J. Joseph Kim
• 金额: $ 9.99万
• 依托单位: VIRAL GENOMIX, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584499
• 关键词: antibacterial agents; antitoxins; cytoprotection; drug design /synthesis /production; drug screening /evaluation; immunization; laboratory mouse; lipopolysaccharides; septicemia; staphylococcal enterotoxin; toxin

DESCRIPTION (provided by applicant): Sepsis or septic shock is a complex cascade of adverse host systemic inflammatory responses induced by infection. Severe sepsis is the most common type found in the intensive care unit (ICU) and it is a common, frequently fatal and expensive disease. In fact, severe sepsis is the number one cause of death in the non-coronary ICU and the 11th leading cause of death overall in the United States (US). Recent studies report that there are at least 750,000 new cases of severe sepsis annually in the US with more than 2,000 new cases per day. Progression of sepsis can lead to organ dysfunction and ultimately death. Mortality from severe sepsis ranges from 30 to 50 percent or greater. The applicants have developed a therapeutic agent, Adeno-Vpr, which they believe has important therapeutic qualities relevant to the pathogenesis of severe sepsis. Viral Genomix, Inc. has a diverse and proprietary patent position on the use of Adeno-Vpr to treat sepsis and other inflammatory diseases. Successful completion of these Phase I studies will result in the demonstration of feasibility for using Adeno-Vpr as a novel drug to treat sepsis. The investigators will test their hypothesis through the conduct of three specific aims using staphylococcal enterotoxin B (SEB) and lipopolysaccharides (LPS) as model toxins from Gram-positive and Gram-negative bacteria, respectively. There are three specific aims: (1) to test the protective effects of Adeno-Vpr in lethal SEB and LPS challenge models in mice; (2) to investigate timing of injections Vs protective effects of Adeno-Vpr in SEB and LPS challenge models in mice; and (3) to test the protective effects of Adeno-Vpr in mice against polybacterial sepsis challenge using the cecal ligation and puncture (CLP) model. This project will test the hypothesis that Adeno-Vpr will be effective at preventing morbidity and mortality from toxin induced cytokine storm and sepsis in a murine model system. Successful completion of this proof-of-concept funding in this Phase I program will enable further testing of the applicant organization's drug candidate for sepsis in a Phase II program.

描述（由申请人提供）：脓毒症或脓毒性休克是由感染引起的不良宿主全身炎症反应的复杂级联反应。严重脓毒症是重症监护室（ICU）最常见的类型，它是一种常见的，经常致命的和昂贵的疾病。事实上，严重脓毒症是非冠状动脉重症监护病房的头号死亡原因，也是美国第11大死亡原因。最近的研究报告称，美国每年至少有75万新发严重败血症病例，每天新发病例超过2000例。败血症的进展可导致器官功能障碍并最终导致死亡。严重败血症的死亡率为30%至50%或更高。