Dual Use Therapeutics for Cryptosporidiosis, Toxoplasmosis, and Neosporosis

隐孢子虫病、弓形虫病和新孢子虫病的双重用途疗法

基本信息

批准号：
9306892
负责人：
WESLEY C VAN VOORHIS
金额：
$ 35.81万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2014-09-24 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9306892
关键词：
2 year old Agriculture Animal Diseases Animal Model Animals Binding Sites Blood Cattle Cell Culture Techniques Cell Proliferation Chemicals Child Childhood Clinical Congenital Abnormality Cryptosporidiosis Cryptosporidium Cryptosporidium parvum Diarrhea Digit structure Domestic Animals Dose Drug Design Drug Kinetics Economics Epidemic Excretory function Feces Fetus Funding Gatekeeping Glycine Goals Goat Health Human Immunocompromised Host Industry Infection Kilogram Lead Link Livestock Mammalian Cell Metabolism Milk Modeling Mus National Institute of Allergy and Infectious Disease Neospora caninum Newborn Infant Pharmaceutical Preparations Phosphotransferases Preclinical Testing Pregnant Women Primary Infection Property Protein Kinase Relapse Rodent Model Ruminants Sampling Sheep Structure Testing Therapeutic Therapeutic Uses Time Tissues Toxic effect Toxicity Tests Toxicology Toxoplasma gondii Toxoplasmosis abortion absorption animal efficacy base calcium-dependent protein kinase clinical candidate drug candidate drug development drug metabolism drug testing efficacy study efficacy testing fetal in vivo kinase inhibitor malformation meetings mortality mouse model novel therapeutics pharmacokinetic model pre-clinical preclinical study pregnant prevent public health relevance scale up wasting

项目摘要

DESCRIPTION (provided by applicant): New drugs are urgently needed for cryptosporidiosis and toxoplasmosis for human and domestic livestock use. Cryptosporidiosis causes wasting diarrhea in humans and calves. Toxoplasmosis is an important cause of fetal malformations and abortions in humans and domestic livestock. In addition, an effective drug is also needed for veterinary use for neosporosis, the cause of epidemic abortions in livestock. This project follows on our successful hit-to-lead drug development project, targeting protozoan Calcium Dependent Protein Kinases (CDPKs). We now have two promising pre-clinical drug candidates that show activity in mouse models of cryptosporidiosis, toxoplasmosis and neosporosis, and thus are of great potential value for both veterinary and human health. The goal of this project will be to conduct efficacy, pharmacokinetic (PK), and toxicity testing of our novel therapeutics in agriculturally-important domestic animals (cattle and sheep) to show efficacy for animal diseases and to also gather information for the preclinical drug package for human use. We will scale-up the compounds to the near kilogram quantity, test their efficacy in sheep models of toxoplasmosis and neosporosis, and in a calf model of cryptosporidiosis. In the end of this project, the goal is to have a preclinical drug candidate and one or two backups to advance to final preclinical testing and IND/NADA registration for veterinary and human use.

描述（由申请人提供）：迫切需要用于人类和家畜使用的治疗隐孢子虫病和弓形虫病的新药。隐孢子虫病会导致人类和犊牛消耗性腹泻。弓形体病是人类和家畜胎儿畸形和流产的重要原因。此外，兽医还需要一种有效的药物来治疗新孢子虫病，这是导致牲畜流行性流产的原因。该项目是我们成功的先导药物开发项目的后续，该项目针对原生动物钙依赖性蛋白激酶 (CDPK)。我们现在有两种有前途的临床前候选药物，它们在隐孢子虫病、弓形虫病和新孢子虫病小鼠模型中显示出活性，因此对兽医和人类健康都具有巨大的潜在价值。该项目的目标是在重要农业家畜（牛和羊）中对我们的新疗法进行功效、药代动力学 (PK) 和毒性测试，以显示对动物疾病的功效，并收集临床前药物包的信息供人类使用。我们将把这些化合物的数量扩大到接近公斤，并在绵羊弓形虫病和新孢子虫病模型以及小牛隐孢子虫病模型中测试其功效。在该项目结束时，目标是拥有一个临床前候选药物和一两个备份，以推进最终的临床前测试以及兽医和人类使用的 IND/NADA 注册。