Advancing New Drug Regimens for MDR/XDR TB

推进耐多药/广泛耐药结核病的新药物治疗方案

基本信息

批准号：
7988845
负责人：
ERIC L NUERMBERGER
金额：
$ 38.98万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-15 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7988845
关键词：
Academia Animal Model Antimycobacterial Agents Bacteria Bacterial Proteins Biological Models Carbapenems Cell Culture System Cell Culture Techniques Cell Wall Characteristics Chronic Clavulanate Clinical Clinical Trials Cultured Cells Data Development Dose Drug Combinations Drug Kinetics Drug Resistant Tuberculosis Drug resistance Drug usage Drug-sensitive Emergency Situation Ensure Ethambutol Ethylenediamines Extreme drug resistant tuberculosis Future Goals Human Imipenem In Vitro Infection Institution Laboratories Lactamase Liquid substance Marketing Measures Meropenem Modeling Mus Mycobacterium tuberculosis New Agents Oral Oxazolidinones Pharmaceutical Preparations Pharmacologic Substance Plasma Prevention Prodrugs Program Development Protein Biosynthesis Protein Synthesis Inhibitors Regimen Relapse Resistance Staging Sterilization Techniques Testing Tissues Tuberculosis Vertebral column Whole Blood World Health combat drug candidate drug development extracellular global health improved inhibitor/antagonist innovation killings mathematical model member mouse model novel pharmacodynamic model prevent research study resistant strain success tuberculosis drugs tuberculosis treatment

项目摘要

DESCRIPTION (provided by applicant): The global emergence of highly drug resistant tuberculosis (MDR and XDR TB) poses a serious and growing threat to world health. New classes of TB drugs are urgently needed to combat these infections, but new regimens comprised of 2 or more members of such new classes of TB drugs are thought to have the greatest chances of long-term success. The current paradigm is to study new drugs individually, but this does not inform the development of new regimens. Moreover, the perceived lack of a viable market has deterred many companies from developing new drugs for TB. This project is a unique partnership between big pharma, biotech and academia that will examine a novel 3-drug combination of new agents in which 2 drugs attack different components of the bacterial cell wall and the third blocks bacterial protein synthesis. Two of the drugs are currently in separate clinical development programs for a TB indication. The third is in clinical development for indications other than TB and would not likely be developed for TB without independent support. This proposed drug combination will be studied intensively to with regard its ability to rapidly kill TB bacteria and prevent emergence of resistance. These characteristics as well as the optimal combinations and dosing regimens will be determined using innovative liquid culture and cell culture systems and a well established mouse model in an effort integrated with sophisticated mathematical modeling techniques. Additional new agents in clinical development may be incorporated as the project evolves. The goal is to identify potent drug combinations that are likely to be safe and effective and that could be subsequently tested in human clinical trials. New drug regimens comprised of 2 or more new drug classes are urgently needed to combat the serious and growing global health emergency posed by highly drug resistant tuberculosis (MDR and XDR TB). This project proposes a unique partnership between a major pharmaceutical company, a small biotech company and 2 academic institutions to examine a novel combination of 3 new agents expected to have a synergistic killing effect against TB bacteria. The goal is to identify potent drug combinations that are likely to be safe and effective and that could be subsequently tested in human clinical trials.

描述（由申请人提供）：全球出现的高度耐药结核病（MDR 和 XDR TB）对世界健康构成了严重且日益严重的威胁。迫切需要新型结核病药物来对抗这些感染，但由两种或多种此类新型结核病药物组成的新疗法被认为最有可能获得长期成功。目前的范式是单独研究新药，但这并不能为新疗法的开发提供信息。此外，由于缺乏可行的市场，许多公司不敢开发结核病新药。该项目是大型制药公司、生物技术和学术界之间的独特合作伙伴关系，将研究一种新型的三药组合新药，其中两种药物攻击细菌细胞壁的不同成分，第三种药物阻止细菌蛋白质合成。其中两种药物目前正处于针对结核病适应症的单独临床开发计划中。第三个是针对结核病以外的适应症的临床开发，如果没有独立支持，不太可能针对结核病进行开发。我们将深入研究这种拟议的药物组合，以确定其快速杀死结核菌和防止耐药性出现的能力。这些特征以及最佳组合和给药方案将使用创新的液体培养和细胞培养系统以及完善的小鼠模型并与复杂的数学建模技术相结合来确定。随着项目的发展，可能会纳入临床开发中的其他新药物。目标是确定可能安全有效且随后可以在人体临床试验中进行测试的有效药物组合。迫切需要由 2 种或更多新药物类别组成的新药物治疗方案，以应对高度耐药结核病（耐多药结核病和广泛耐药结核病）造成的严重且日益严重的全球卫生紧急情况。该项目提议一家大型制药公司、一家小型生物技术公司和两家学术机构之间建立独特的合作伙伴关系，以研究 3 种新药物的新型组合，预计对结核菌具有协同杀灭作用。目标是确定可能安全有效且随后可以在人体临床试验中进行测试的有效药物组合。