DEVELOPMENT OF DRUGS FOR CRYPTOSPORIDIUM INFECTION

目前治疗与艾滋病相关的机会性感染的治疗方法 获得性免疫缺陷综合症(AIDS)要么剧毒， 极其昂贵或略微有效的。因为这些感染 在艾滋病患者中产生显著的发病率和死亡率， 国家过敏和传染病研究所已经资助了几个 促进发现和开发新的治疗方法的计划 艾滋病相关机会性感染的治疗。在 发展治疗分部，这是通过提供 合同资源，用于确定和开发潜在的新药。在… 目前还没有推荐的治疗隐孢子虫感染的方法。 细小，部分原因是缺乏体外培养系统和小 适用于药物评价的动物模型。此操作的第一阶段 该项目将支持三个机构在体外和 活体测试系统。此后，在计划的第二阶段，一个或多个 这些机构将被选中，以应用他们的系统进行评估 潜在新药对隐孢子虫的疗效。文化 因此，通过这些合同开发的系统和动物模型将 为NIAID提供必要的资源，以提供关键支持 由研究人员发起的药物发现，以刺激私营部门 赞助具有展示功效的化合物，并选择最佳 临床试验的候选药物。 上述合同的第一阶段将制定和验证 地塞米松抑制C57BL/6N小鼠慢性炎症模型的建立 隐孢子虫病。如果被选中参加计划的第二阶段，承包商 将利用DEX小鼠模型来筛选活性药理物质 抗隐孢子虫病，并进一步进行初步毒性和 药代动力学评估和优化药物剂量和给药途径。 承包商将进一步测试各种电池线的能力 支持寄生虫的体外生长并进行初步的化合物筛选 对抗寄生虫。

Current therapies to treat opportunistic infections associated with the Acquired Immunodeficiency Syndrome (AIDS) are either highly toxic, extremely expensive or marginally effective. Since these infections produce significant morbidity and mortality in patients with AIDS, the National Institute of Allergy and Infectious Diseases has funded several programs to facilitate discovery and development of novel therapies for the treatment of AIDS-related opportunistic infections. Within the Developmental Therapeutic Branch, this has been accomplished by providing contract resources for identifying and developing potential new drugs. At present there is no recommended therapy for infection with Cryptoslporidium parvum, in part, because of the lack of in vitro culture systems and small animal models that are suitable for drug evaluations. Phase 1 of this project will support three agencies in the development of in vitro and in vivo test systems. Thereafter in Phase 2 of the program, one or more of these agencies will be selected to apply their systems toward evaluating the efficacy of potential new drugs against Cryptosporidium. The culture systems and animal models developed through these contracts will therefore provide NIAID with the necessary resources to provide critical support for investigator-initiated drug discovery, to stimulate private sector sponsorship of compounds with demonstrated efficacy, and to select the best drug candidates for clinical trials. Phase I of the contract indicated above will develop and validate the dexamethasone (DEX)-suppressed C57BL/6N mouse as a model for chronic cryptosporidiosis. If selected for Phase 2 of the program the contractor will utilize the DEX mouse model to screen pharmacologic agents active against Cryptosporidiosis, and furthermore conduct initial toxicity and pharmacokinetic assessments and optimize drug dosages and delivery routes. The contractor will furthermore test various cell lines in their ability to support parasite growth in vitro and perform initial compound screening against the parasite.