Response Therapies for MDR-TB

描述（由申请人提供）：本对RFA 05-019的响应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州洛夫兰市麦可斯研究所。这一申请的目的具有应用科学基础，包括优先考虑新的有希望的药物，以及有希望作为暴露后疫苗的分枝杆菌抗原，以处理故意使个人暴露于可能对所有已知常规使用的结核病药物具有潜在耐药性的C类病原体结核分枝杆菌分离物。一些有前途的先导化合物以及新的研究药物，如PA-824，最近已经在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项目中合作，并提供已知的对药物敏感的结核分枝杆菌有活性的其他化合物。在平行研究中，我们还将利用我们在结核病疫苗研究方面久经考验的专业知识，根据本提案中详细说明的表明这是可以实现的早期结果，处理开发一种快速活性暴露后疫苗这一更困难的问题。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TH1反应。一旦确定了新的候选药物，我们将根据我们的结果对它们与新的化疗方案一起进行测试。安全测试问题、毒理学测试和导致GMP生产的工艺开发也计划在该计划的后期阶段进行。

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.