Response Therapies for MDR-TB

耐多药结核病的反应治疗

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：这种对RFA 05-019的反应来自科罗拉多州立大学的分枝杆菌研究实验室，西雅图的传染病研究所和科罗拉多州Loveland的Mycos Research。该应用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，以应对个人故意暴露于孤立的结核分枝杆菌的分析，这是一种潜在的常规药物，可能会抵抗所有常规的药物。最近在CSU测试了几种有希望的铅化合物以及新的研究药物，例如PA-824，并将在该计划中针对MDR菌株进行进一步探讨。此外，三家领先的制药公司都表示愿意在该计划中进行合作，并提供已知已经活跃于药物敏感的结核分枝杆菌的其他化合物。在平行研究中，我们还将在结核病疫苗研究方面借用我们的可靠专业知识，以应对开发快速活跃的暴露后疫苗的更困难的问题，这是基于本提案中详细介绍的早期结果，表明可以实现这一点。这些是基于蛋白质的，此外，我们将测试选择用于有效TH1反应的新一代佐剂。一旦确定了新的候选者，他们将根据我们的结果对新化疗方案进行测试。还计划在此拟议计划的后期阶段，还计划了安全测试问题，毒理学测试和过程开发导致GMP生产的过程。