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

• 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
• 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

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）对世界卫生构成了严重且日益严重的威胁。抗击这些感染迫切需要新型结核病药物，但由两种或两种以上这类新型结核病药物组成的新方案被认为最有可能取得长期成功。目前的模式是单独研究新药，但这并没有为新疗法的发展提供信息。此外，人们认为缺乏可行的市场阻碍了许多公司开发结核病新药。该项目是大型制药公司、生物技术公司和学术界之间的独特合作伙伴关系，将研究一种新的三药组合药物，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的合成。其中两种药物目前正分别处于结核病适应症的临床开发项目中。第三种是针对结核病以外适应症的临床开发，如果没有独立的支持，不太可能针对结核病开发。将对这一拟议的药物组合进行深入研究，以了解其快速杀死结核细菌和防止出现耐药性的能力。这些特性以及最佳组合和给药方案将通过创新的液体培养和细胞培养系统以及一个完善的小鼠模型来确定，该模型将与复杂的数学建模技术相结合。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的强效药物组合，并可随后在人体临床试验中进行测试。