Novel Therapeutic Approaches For Treatment of Intestinal Inflammation

治疗肠道炎症的新方法

基本信息

  • 批准号:
    9925209
  • 负责人:
  • 金额:
    $ 34.09万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-07-01 至 2023-04-30
  • 项目状态:
    已结题

项目摘要

Summary The two most common forms of inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis, affect approximately 1.4 million people in the United States. The etiology of IBD is unclear, yet aberrant innate and adaptive immune responses directed towards the commensal microbiota are believed to underlie disease pathogenesis. Numerous pro-inflammatory factors contribute to disease severity and targeting some of these factors has proven effective in the treatment of IBD patients. TNFα in particular plays a crucial role as a pro- inflammatory mediator in the pathogenesis of IBD and the anti-TNFα monoclonal antibody, infliximab, is now successfully used in the clinic to treat human IBD. However, anti-TNFα therapy is only effective in a subset of IBD patients and concerns remain regarding adverse effects, such as cancer and opportunistic infections. The observed adverse effects are mainly due to the lack of targeted treatment and the “over dosage” that is usually inherent to systemic drug administration. More recently, a monoclonal antibody targeting IL-12 and IL-23, ustekinumab, was shown to be effective in IBD patients, especially those in which anti-TNFα therapy had previously failed. Thus, treatment of human IBD may be optimized by novel delivery regimens that allow for targeted, low-dose inhibition of both TNF-α and IL-12/23. We have demonstrated that oral administration of nanoparticles loaded with TNFα siRNA and encapsulated in an alginate-chitosan hydrogel can be efficiently targeted to the colon without toxicity and reduce intestinal inflammation in a mouse model. Our exciting preliminary data demonstrate that specific targeting of nanoparticles containing siRNA to intestinal antigen presenting cells may enhance the beneficial effects of this novel therapeutic approach. In the course of these studies, we also discovered that inhibition of pro-inflammatory cytokines can have the unexpected side effect of inhibiting critical wound-healing factors, such as IL-22. These finding have led us to propose that nanoparticle-mediated manipulation of TNFα, IL-12/23 and IL-22 limits intestinal inflammation and promotes wound healing during IBD. These novel strategies aimed at locally inhibiting key pro-inflammatory cytokines while simultaneously promoting wound healing may contribute to the development of improved therapies for the treatment of human IBD.
总结

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Timothy L Denning其他文献

Timothy L Denning的其他文献

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{{ truncateString('Timothy L Denning', 18)}}的其他基金

IL-36 cytokines and gut immunity
IL-36 细胞因子和肠道免疫
  • 批准号:
    10302264
  • 财政年份:
    2019
  • 资助金额:
    $ 34.09万
  • 项目类别:
IL-36 cytokines and gut immunity
IL-36 细胞因子和肠道免疫
  • 批准号:
    10534223
  • 财政年份:
    2019
  • 资助金额:
    $ 34.09万
  • 项目类别:
IL-36 cytokines and gut immunity
IL-36 细胞因子和肠道免疫
  • 批准号:
    9887444
  • 财政年份:
    2019
  • 资助金额:
    $ 34.09万
  • 项目类别:
Fecal exosomes as a source of miRNA biomarkers for diagnosing the degree of colitis and as a drug delivery system to reduce colitis
粪便外泌体作为 miRNA 生物标志物的来源,用于诊断结肠炎的程度,并作为减少结肠炎的药物输送系统
  • 批准号:
    9460216
  • 财政年份:
    2017
  • 资助金额:
    $ 34.09万
  • 项目类别:
Fecal exosomes as a source of miRNA biomarkers for diagnosing the degree of colitis and as a drug delivery system to reduce colitis
粪便外泌体作为 miRNA 生物标志物的来源,用于诊断结肠炎的程度,并作为减少结肠炎的药物输送系统
  • 批准号:
    9982320
  • 财政年份:
    2017
  • 资助金额:
    $ 34.09万
  • 项目类别:
Fecal exosomes as a source of miRNA biomarkers for diagnosing the degree of colitis and as a drug delivery system to reduce colitis
粪便外泌体作为 miRNA 生物标志物的来源,用于诊断结肠炎的程度,并作为减少结肠炎的药物输送系统
  • 批准号:
    9750698
  • 财政年份:
    2017
  • 资助金额:
    $ 34.09万
  • 项目类别:
Novel Therapeutic Approaches For Treatment of Intestinal Inflammation
治疗肠道炎症的新方法
  • 批准号:
    9232271
  • 财政年份:
    2017
  • 资助金额:
    $ 34.09万
  • 项目类别:
Intestinal Antigen Presenting Cells and Mucosal Immunity
肠道抗原呈递细胞和粘膜免疫
  • 批准号:
    8727543
  • 财政年份:
    2013
  • 资助金额:
    $ 34.09万
  • 项目类别:
Intestinal Antigen Presenting Cells and Mucosal Immunity
肠道抗原呈递细胞和粘膜免疫
  • 批准号:
    8579023
  • 财政年份:
    2013
  • 资助金额:
    $ 34.09万
  • 项目类别:
Intestinal Antigen Presenting Cells and Mucosal Immunity
肠道抗原呈递细胞和粘膜免疫
  • 批准号:
    8890154
  • 财政年份:
    2013
  • 资助金额:
    $ 34.09万
  • 项目类别:

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