Development and Treatment of Pre-Clinical EHEC Models with HUS

HUS 临床前 EHEC 模型的开发和治疗

基本信息

  • 批准号:
    8578280
  • 负责人:
  • 金额:
    $ 38.47万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-08-01 至 2017-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Enterohemorrhagic Shiga toxin-producing E. Coli (EHEC) bacteria are NIAID Biodefense Priority B pathogens and a global health problem. The E. Coli O157:H7 strain is most common and is a recent contaminant of hamburger, spinach, bean sprouts and other foods causing multi-state and multi-country outbreaks. The US burden is ~176,000 infections annually (est. 150 million globally) with significant morbidity, particularl acute kidney injury in young children and the elderly. The hemorrhagic colitis usually resolves, but some patients progress to potentially lethal hemolytic uremic syndrome (HUS), as well as neurologic, pulmonary and cardiac complications. Long-term renal sequelae occur in 25-36% of patients who survive diarrhea- associated HUS. Bacterial toxins (Stx1,Stx2) drive organ damage, yet toxin-specific therapeutics are not available because drug development is hindered by lack of animal models that recapitulate human symptoms, lack of drugs that neutralize toxin within cells, and lack of biomarkers that predict HUS risk or report early renal injury. We have developed the only animal models that develop Stx-induced HUS. Using Rescue Protocols, we will use these models to test the hypothesis that targeting the toxins in the blood and already within cells with adjunctive therapeutics will prevent or mitigate development of Stx-induced HUS, and that Stx- induced biomarkers can report organ injury to identify those at high risk for HUS. We predict that targeting toxins in one or both compartments will reduce acute kidney injury and minimize disease severity. Intracellular toxins will be targeted with custom designed cell permeable peptides (Aim1) and intravascular toxin will be targeted with a patented humanized anti-Stx2 monoclonal antibody (Aim2). Studies are designed to maximize delayed administration of drug while maintaining efficacy. New and established biomarkers will be correlated with experimental clinical results to identify molecules that report early and sustained kidney injury, and HUS risk. Our combination of clinically relevant animal models with systemic and intracellular toxin targeting compounds is a powerful approach to move the field forward toward targeted patient treatment.
性状(由申请方提供):产肠出血性滋贺毒素E.大肠杆菌(EHEC)是NIAID生物防御优先级B病原体,是全球健康问题。急诊大肠杆菌O 157:H7菌株是最常见的,是最近汉堡包,菠菜,豆芽和其他食品的污染物,造成多个州和多个国家的爆发。美国的负担是每年约176,000例感染(估计。全球1.5亿),发病率很高,特别是幼儿和老年人的急性肾损伤。出血性结肠炎通常会消退,但有些患者会发展为潜在致命的溶血性尿毒综合征(HUS),以及神经系统、肺和心脏并发症。25-36%的腹泻相关HUS存活患者发生长期肾脏后遗症。细菌毒素(Stx 1,Stx 2)驱动器官损伤,但毒素特异性治疗方法不可用,因为药物开发受到缺乏重现人类症状的动物模型,缺乏中和细胞内毒素的药物以及缺乏预测HUS风险或报告早期肾损伤的生物标志物的阻碍。我们已经开发出唯一的动物模型,发展Stx诱导的HUS。使用Rescue Protocols,我们将使用这些模型来测试以下假设:靶向血液中的毒素和已经在细胞内的毒素,用免疫疗法将预防或减轻Stx诱导的HUS的发展,并且Stx诱导的生物标志物可以报告器官损伤以识别HUS的高风险。我们预测,在一个或两个隔室中靶向毒素将减少急性肾损伤并最大限度地降低疾病的严重程度。细胞内毒素将以定制设计的细胞渗透性肽(Aim 1)为靶点,血管内毒素将以专利的人源化抗Stx 2单克隆抗体(Aim 2)为靶点。研究旨在最大限度地延迟给药,同时保持疗效。新的和已建立的生物标志物将与实验性临床结果相关联,以确定早期和持续报告的分子。 肾损伤和HUS风险。我们将临床相关动物模型与全身和细胞内毒素靶向化合物相结合,是将该领域推向靶向患者治疗的有力方法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Shinichiro Kurosawa其他文献

Shinichiro Kurosawa的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Shinichiro Kurosawa', 18)}}的其他基金

Development and Treatment of Pre-Clinical EHEC Models with HUS
HUS 临床前 EHEC 模型的开发和治疗
  • 批准号:
    8711271
  • 财政年份:
    2013
  • 资助金额:
    $ 38.47万
  • 项目类别:
Development and Treatment of Pre-Clinical EHEC Models with HUS
HUS 临床前 EHEC 模型的开发和治疗
  • 批准号:
    8889621
  • 财政年份:
    2013
  • 资助金额:
    $ 38.47万
  • 项目类别:
Translation of immunologic technologies from basic research into pre-clinical non
免疫学技术从基础研究到临床前非临床研究的转化
  • 批准号:
    7696151
  • 财政年份:
    2009
  • 资助金额:
    $ 38.47万
  • 项目类别:
SHIGA-TOXINS: PRE-CLINICAL ANIMAL MODEL DEVELOPMENT AND THERAPEUTIC TESTING
志贺毒素:临床前动物模型开发和治疗测试
  • 批准号:
    7492271
  • 财政年份:
    2007
  • 资助金额:
    $ 38.47万
  • 项目类别:
SHIGA-TOXINS: PRE-CLINICAL ANIMAL MODEL DEVELOPMENT AND THERAPEUTIC TESTING
志贺毒素:临床前动物模型开发和治疗测试
  • 批准号:
    8129795
  • 财政年份:
    2007
  • 资助金额:
    $ 38.47万
  • 项目类别:
SHIGA-TOXINS: PRE-CLINICAL ANIMAL MODEL DEVELOPMENT AND THERAPEUTIC TESTING
志贺毒素:临床前动物模型开发和治疗测试
  • 批准号:
    7324405
  • 财政年份:
    2007
  • 资助金额:
    $ 38.47万
  • 项目类别:
SHIGA-TOXINS: PRE-CLINICAL ANIMAL MODEL DEVELOPMENT AND THERAPEUTIC TESTING
志贺毒素:临床前动物模型开发和治疗测试
  • 批准号:
    7932122
  • 财政年份:
    2007
  • 资助金额:
    $ 38.47万
  • 项目类别:
SHIGA-TOXINS: PRE-CLINICAL ANIMAL MODEL DEVELOPMENT AND THERAPEUTIC TESTING
志贺毒素:临床前动物模型开发和治疗测试
  • 批准号:
    7674772
  • 财政年份:
    2007
  • 资助金额:
    $ 38.47万
  • 项目类别:
PRIMATE MODEL AND PATHOGENESIS OF ANTHRAX SEPSIS
灵长类动物模型和炭疽脓毒症的发病机制
  • 批准号:
    6867189
  • 财政年份:
    2005
  • 资助金额:
    $ 38.47万
  • 项目类别:
PLASMA SEPCR LEVELS IN PATIENTS AFTER MYOCARDIAL INFARCTION
心肌梗死后患者的血浆 SEPCR 水平
  • 批准号:
    7203332
  • 财政年份:
    2005
  • 资助金额:
    $ 38.47万
  • 项目类别:

相似海外基金

Acute Kidney Failure in a Cancer ICU
癌症 ICU 中的急性肾衰竭
  • 批准号:
    7034020
  • 财政年份:
    2006
  • 资助金额:
    $ 38.47万
  • 项目类别:
Acute Kidney Failure in a Cancer ICU
癌症 ICU 中的急性肾衰竭
  • 批准号:
    7459945
  • 财政年份:
    2006
  • 资助金额:
    $ 38.47万
  • 项目类别:
Acute Kidney Failure in a Cancer ICU
癌症 ICU 中的急性肾衰竭
  • 批准号:
    7922716
  • 财政年份:
    2006
  • 资助金额:
    $ 38.47万
  • 项目类别:
Acute kidney failure: investigation and treatment of ki dney cell injury
急性肾衰竭:肾细胞损伤的调查和治疗
  • 批准号:
    nhmrc : 901011
  • 财政年份:
    1990
  • 资助金额:
    $ 38.47万
  • 项目类别:
    NHMRC Project Grants
Acute kidney failure: new methods of investigation and treatment
急性肾衰竭:研究和治疗的新方法
  • 批准号:
    nhmrc : 891081
  • 财政年份:
    1989
  • 资助金额:
    $ 38.47万
  • 项目类别:
    NHMRC Project Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了