权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterizing new nematode-specific drug targets to eliminate the reservoir for human toxocariasis

表征新的线虫特异性药物靶点以消除人类弓蛔虫病的储存库

基本信息

批准号：
9882952
负责人：
Matthew Brewer
金额：
$ 19.13万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9882952
关键词：
ABCB1 gene Adult Animals Anthelmintics Antibodies Antiparasitic Agents Binding Biological Assay Canis familiaris Chemosensitization Communicable Diseases Data Disease Drug Efflux Drug Targeting Drug Tolerance Drug resistance Environment Future Gene Expression Glycoproteins Goals Hair Human In Vitro Ingestion Lactones Larva Larva Migrans Location Maps Mediating Messenger RNA Mission Modeling Molecular Target Mus Nematoda Orthologous Gene Outcome P-Glycoprotein Parasites Parasitic nematode Performance Permeability Pharmaceutical Preparations Pharmacology Pharmacotherapy Poverty Quantitative Reverse Transcriptase PCR Refractory Resistance Techniques Testing Tissues Toxocara Toxocara canis Toxocariasis United States National Institutes of Health Visceral efflux pump egg glutamate-gated chloride channel inhibitor/antagonist neglect new therapeutic target novel prevent receptor

项目摘要

Project Summary Toxocara canis causes visceral and ocular larval migrans in humans. The reason why this disease cannot be eliminated is because tissue-dwelling larvae persist in the animal reservoir (dogs) where they tolerate anthelmintic treatment, and the mechanism for drug tolerance is unknown. Our hypothesis is that T. canis larvae evade drug treatment by effluxing antiparasitic drugs with permeability glycoproteins (P- glycoproteins) that efflux anthelmintics. In this application we propose to 1) record the repertoire of P- glycoprotein gene expression in T. canis, 2) map the precise tissues where P-glycoproteins are expressed, 3) demonstrate induction of P-glycoprotein activity by anthelmintic drugs, 4) characterize the unique pharmacology of T. canis P-glycoprotein, and 5) discover nematode-specific P-glycoprotein inhibitors that enhance the performance of antiparasitic drugs.

项目摘要犬弓首线虫引起人类内脏和眼部幼虫移行。这种疾病之所以不能被淘汰是因为组织居住的幼虫坚持在动物水库（狗），他们容忍驱虫治疗，药物耐受性的机制是未知的。我们假设T. Canis 幼虫通过渗透性糖蛋白（P- 糖蛋白）流出驱虫剂。在本申请中，我们提出1）记录P的库，糖蛋白基因在T.犬，2）绘制P-糖蛋白表达的精确组织， 3)证明驱虫药诱导P-糖蛋白活性，4）表征独特的药理学的T.犬P-糖蛋白，和5）发现线虫特异性P-糖蛋白抑制剂增强抗寄生虫药物的效果。