Response Therapies for MDR-TB

耐多药结核病的反应治疗

• 批准号: 7484228
• 负责人: IAN M ORME
• 金额: $ 113.19万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7484228
• 关键词: Adjuvant; Aerosols; Animal Model; Animals; Antigens; Area; Basic Science; Cell Wall; Chemical Structure; Chemotherapy-Oncologic Procedure; Class; Clinical Trials; Colorado; Complex; Contracts; Development; Dose; Drug Formulations; Drug-sensitive; Evaluation; Faculty; Foundations; Funding; Generations; Genus Mycobacterium; Growth; Guanosine Monophosphate; Housing; In Vitro; Individual; Infectious Diseases Research; Instruction; Investigational Drugs; Laboratory Research; Lead; Modeling; Multiple drug resistant Mycobacteria Tuberculosis; Mycobacterium tuberculosis; Numbers; Organism; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Process; Production; Proteins; Proteome; Purpose; Research; Research Institute; Research Personnel; Resistance; Safety; Screening procedure; Staging; Students; Testing; Toxic effect; Toxicology; Translating; Treatment Protocols; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Universities; Vaccination; Vaccine Research; Vaccines; Virulent; Work; base; chemotherapy; drug discovery; experience; immunogenicity; in vivo; interest; killings; mycobacterial; novel; novel strategies; novel therapeutics; novel vaccines; pathogen; programs; prophylactic; research clinical testing; response; scale up; tuberculosis drugs; vaccine development; willingness

DESCRIPTION (provided by applicant): This response to RFA 05-019 is from the Mycobacteria Research Laboratories at Colorado State University, the Infectious Disease Research Institute in Seattle, and Mycos Research, Loveland, Colorado. The purpose of this application has an applied scientific basis and consists of prioritization of new promising drugs, as well as mycobacterial antigens that have promise as post-exposure vaccines, to deal with a deliberate exposure of individuals to an isolate of Mycobacterium tuberculosis, a Class C pathogen, that might potentially be resistant to all known conventionally used TB drugs. Several promising lead compounds as well new investigational drugs such as PA-824 have recently been tested at CSU and will be explored further in this program against MDR strains. In addition, three leading pharmaceutical companies have all expressed their willingness to collaborate in this program and to provide additional compounds already known to be active against drug sensitive M. tuberculosis. In parallel studies we will also lend our proven expertise in TB vaccine research to deal with the more difficult issue of developing a rapidly active post-exposure vaccine, based upon early results detailed in this proposal indicating that this can be achieved. These are protein based, and in addition we will test a new generation of adjuvants selected for potent TH1 responses. Once new candidates are identified they will be tested in conjunction with new chemotherapy regimens based upon our results. Safety testing issues, toxicology testing, and process development leading to GMP production are also planned for the later stages of this proposed program.

描述（由申请方提供）：本RFA 05-019回复来自科罗拉多州立大学分枝杆菌研究实验室、西雅图传染病研究所和科罗拉多洛夫兰的Mycos研究所。本申请的目的具有应用科学基础，包括优先考虑新的有前途的药物，以及有望作为暴露后疫苗的分枝杆菌抗原，以处理个体故意暴露于结核分枝杆菌分离株（C类病原体）的情况，该分离株可能对所有已知的常规使用的TB药物具有耐药性。几种有前景的先导化合物以及新的研究药物（如PA-824）最近已在CSU进行了测试，并将在该项目中进一步探索耐多药菌株。此外，三家领先的制药公司都表示愿意在该计划中合作，并提供已知对药物敏感的M.结核在平行研究中，我们还将根据本提案中详细说明的早期结果，提供我们在结核病疫苗研究方面的成熟专业知识，以处理开发快速活性暴露后疫苗这一更困难的问题，表明这是可以实现的。这些都是基于蛋白质的，此外，我们将测试新一代的佐剂选择有效的TH 1反应。一旦确定了新的候选人，他们将根据我们的结果与新的化疗方案一起进行测试。安全性测试问题、毒理学测试和导致GMP生产的工艺开发也计划在该拟议项目的后期阶段进行。