Optimized Combination Antimalarial Drug Therapy

描述（由申请人提供）：迫切需要快速确定临床使用的抗疟疾药物组合并对其进行优先排序。联合治疗最有可能减少新耐药现象出现的频率，我们的初步数据表明，我们的新方法可以迅速识别出数十种以前未被认识到的具有高度协同作用的药物组合。我们将利用五个联合实验室相当多的互补专业知识，确定、优先考虑和优化耐药恶性疟原虫疟疾的新型联合药物治疗。在这项工作中，我们将利用国家高级转化科学中心（NCATS）最先进的高通量筛选能力，以及最近完善的体外装置，使恶性疟原虫暴露于可编程的、动态变化的药物浓度中。我们还将利用创新的药效学小鼠疟疾模型验证48小时寄生虫减少和28天治愈的增强作用。

DESCRIPTION (provided by applicant): There is an immediate and dire need to rapidly identify and prioritize antimalarial drug combinations for clinical use. Combination therapy has the best chance of reducing the frequency at which new drug resistance phenomena emerge, and our preliminary data suggest that dozens of previously unrecognized drug combinations with high degrees of synergy can be rapidly identified by our new approach. We will leverage the considerable complementary expertise of five consortium laboratories to identify, prioritize and optimize novel combination drug therapy for drug resistant Plasmodium falciparum malaria. In this effort we will use state of the art high throughput screening capabilities of the National Center for Advanced Translational Science (NCATS), as well as a recently perfected in vitro apparatus that exposes P. falciparum to programmable, dynamically changing drug concentrations. We will also validate potentiation of both 48 hr parasite reduction and 28 day cure using an innovative pharmacodynamic mouse malaria model.