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Optimized Combination Antimalarial Drug Therapy

优化的抗疟药物联合疗法

基本信息

批准号：
8707702
负责人：
PAUL D. ROEPE
金额：
$ 105.51万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-15 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8707702
关键词：
Acoustics Address Animal Model Animals Antimalarials Antimicrobial Resistance Artemisinins Chemosensitization Clinic Clinical Combination Drug Therapy Combined Modality Therapy Cytostatics Data Development Disease Dose Drug Combinations Drug Kinetics Drug resistance Drug usage Erythrocytes FDA approved Falciparum Malaria Fiber Frequencies Future In Vitro Individual Kinetics Laboratories Libraries Malaria Measures Methods Modeling Mus Online Systems Parasites Pharmaceutical Preparations Pharmacodynamics Pharmacotherapy Plasmodium falciparum Regimen Relative (related person)Science Staging Technology Testing Translational Research Translations Work artemisinine asexual base drug candidate high throughput screening improved in vivo innovation interest killings novel novel strategies pre-clinical public health relevance quinoline research clinical testing resistant strain response theories user-friendly web site

项目摘要

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.

描述（由申请人提供）：目前迫切需要快速确定和优先考虑临床使用的抗疟药物组合。联合治疗最有可能降低新的耐药现象出现的频率，我们的初步数据表明，我们的新方法可以快速识别数十种以前未被识别的具有高度协同作用的药物组合。我们将利用五个联盟实验室的大量互补专业知识，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疗法。在这项工作中，我们将使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，将恶性疟原虫暴露于可编程的，动态变化的药物浓度。我们还将使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。