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促进发现 和开发治疗艾滋病相关疾病的新疗法 机会性感染。这包括为以下项目提供合同资源 发现和开发潜在的新药，并进行疗效 在动物模型中的评估，这是药物批准的关键组成部分 进程。目前还没有推荐的治疗方法来治疗感染 微小隐孢子虫，部分原因是缺乏体外培养 适用于药物评价的系统和小动物模型。 该项目的第一阶段将支持三个机构制定 体外和体内测试系统。此后，在该计划的第二阶段， 将从这些机构中选择一个或多个机构来应用其系统 对潜在新药治疗的疗效进行评估 隐孢子虫。培养系统和动物模型是通过 这些合同最终将为NIAID提供必要的资源 为研究人员发起的药物发现提供关键支持， 通过示范刺激私营部门对化合物的赞助 疗效，并选择最佳候选药物进行临床试验。 上述合同的第一阶段将对SCID鼠标进行改装 抗隐孢子虫感染候选疗法的初步筛选， 和CD/SPF仔猪模型，用于进一步评估候选药物 在小鼠体内很活跃。药物评估的参数将包括改进 减少临床症状，减少寄生虫脱落，减少寄生虫负荷 和组织病理学。如果选择该计划的第二阶段，则 承包商将系统地将动物模型应用于药物 评估以及开发适合于小学的体外系统 抗培养寄生虫药物的筛选。

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 facilitates discovery and development of novel therapies for the treatment of AIDS-related opportunistic infections. This includes providing contract resources for identifying and developing potential new drugs, and conducting efficacy evaluations in animal models, a critical component in the drug approval process. At present there is no recommended therapy for infection with Cryptosporidium parvum, in part, because of the lack of in vitro culture systems and small animal models that are suitable for drug evaluations. Phase I 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 ultimately 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 adapt the SCID mouse for primary screening of candidate therapies against Cryptosporidium infection, and the CD/SPF piglet model for further evaluating drug candidates that are active in mice. Parameters for drug evaluations will include improvement of clinical symptoms, reduced parasite shedding, and reduced parasite load and tissue pathology. If selected for Phase 2 of the program, the contractor will systematically apply an animal model toward drug evaluations as well as develop in vitro systems suitable for primary screening of drugs against cultured parasites.