ANIMAL MODEL TESTING OF TB DRUGS

结核病药物的动物模型测试

• 批准号: 2296225
• 负责人: IAN M ORME
• 金额: $ 33.34万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2296225
• 关键词: ANIMAL; MODEL; TESTING; TB; DRUGS

The objectives of this contract ar to provide a standardized mechanism for the pre-clinical evaluation of new candidate therapies against Mycobacterium tuberculosis infection. This represents a component of the Division of AIDS' opportunistic infections drug development program and specifically addresses the discovery and development of new therapies to treat tuberculosis, an opportunistic infection which 20 to 30% of HIV patients positive for PPD in the United States are at risk of developing through reactivation of latent infections. Its most common manifestation in AIDS patients is inevitably fatal without appropriate treatment, and may require long-term therapy, i.e. greater than 12 months to lifetime. Treatment-limiting toxicities, lack of potency, and the emergence of resistance have compromised the utility of established drugs. The most significant deficiencies of present therapies are the lack of efficacy against drug resistant strains and the inability to eradicate the latent form of M. tuberculosis which is reactivated when the immune system becomes severely compromised. Specifically, the contractor will evaluate potential therapeutic agents for efficacy against tuberculosis in a mouse model of the infection and will employ defined biologically relevant indicators of disease and infection as endpoints. The test agents will be selected by the Project Officer on the basis of previously determined in vitro activities. The contractor will develop, modify, improve, or otherwise further characterize the animal model or develop other models to expand utility in the evaluation of therapies for the ability to kill quiescent or slowly growing M. tuberculosis. In addition, the contractor will develop alternative models, if necessary, and perform additional studies such as comparison of M. tuberculosis strains and preliminary pharmacokinetic studies. This information will be of benefit to the Government in determining the best candidate therapies for inclusion in clinical trials of new agents against tuberculosis.

该合同AR的目标是提供标准化机制 针对新候选疗法的临床前评估 结核分枝杆菌感染。 这代表了 艾滋病的机会感染药物开发计划和 专门针对新疗法的发现和开发 治疗结核病，这是一种机会感染，其中20％至30％ 美国PPD阳性的患者有发展的风险 通过重新激活潜在感染。 它最常见的表现 在艾滋病中，患者不可避免地是致命的，没有适当的治疗，可以 需要长期治疗，即终生超过12个月。 治疗限制毒性，缺乏效力和出现 耐药性损害了已建立药物的效用。 最多 当前疗法的严重缺陷是缺乏功效 抵抗耐药菌株和无法消除潜在的 结核分枝杆菌的形式，当免疫系统变成时被重新激活 严重妥协。 具体而言，承包商将评估潜在的治疗剂 在感染的小鼠模型中针对结核病的功效，将 使用定义的生物学相关疾病和感染指标 端点。 测试代理将由项目官员选择 先前确定的体外活性的基础。 承包商会 发展，修改，改进或以其他方式进一步表征动物 模型或开发其他模型以扩大评估的实用性 杀死静态或缓慢生长的能力的疗法。 结核。 此外，承包商将开发替代模型， 如有必要，并进行其他研究，例如比较。 结核病菌株和初步药代动力学研究。 这些信息将对政府确定 最佳候选疗法包括在新代理商的临床试验中 反对结核病。