Investigation and Development of New Therapeutic Avenues for Scleroderma

硬皮病新治疗途径的研究和开发

基本信息

  • 批准号:
    8147047
  • 负责人:
  • 金额:
    $ 230.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-30 至 2016-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (Provided by the applicant) Abstract: Currently there is no effective treatment for Scleroderma (systemic sclerosis), an autoimmune disease unresponsive to immunosuppressive therapy. This proposal is based upon the belief that two main barriers exist towards the cure of this disease. First, there is no published technology for isolating unmanipulated pathogenic T cells from patients with autoimmunity. Second, current immunosuppressive medications do not target the correct immune cells in these patients. In order to improve the treatment and survival of these patients it is critical to: identify the role that the immune system plays in this disease, determine the effect that current immunosuppressive therapies have on the patients' autoreactive immune response, identify new therapeutic targets by fully characterizing the autoreactive immune response in scleroderma, and finally to design novel inhibitors to these targets. Our specific hypothesis is that unmanipulated self- reactive T cell clones isolated directly from patients with scleroderma can be used to identify novel therapeutic targets and small molecules capable of selectively binding these pathogenic cells. This hypothesis is based upon the following observations. 1) We have developed a technique to directly isolate pure populations of clonally expanded T cells from patients with autoimmunity. 2) A high affinity ligand for a subpopulation of activated T cells was identified through a combinatorial screening approach. 3) Screening combinatorial libraries has identified inhibitors of key intracellular pathway required for T cell activation. Based upon these observations the experimental focus of this proposal will be to combinatorial libraries to identify novel T cell-inhibiting small molecules and T cell-specific ligands in an attempt to develop a highly effective therapeutic that can target and destroy pathogenic T cells in the setting of scleroderma and other immune mediated diseases of the skin. Public Health Relevance: Normally the immune system functions to fight off infections such as the common cold. In patients with autoimmunity the cells of the immune system damage the tissues and organs of a patient. Some autoimmune diseases respond to immunosuppressive therapy while others are very refractory to treatment. Scleroderma is an autoimmune disease that does not respond to therapy. We will study the immune cells isolated from patients with scleroderma and attempt to identify new therapeutic targets for medications.
描述(由申请人提供) 摘要:硬皮病是一种对免疫抑制治疗无效的自身免疫性疾病,目前尚无有效的治疗方法。这一建议是基于这样一种信念,即在治愈这种疾病方面存在两个主要障碍。首先,目前还没有从自身免疫患者中分离出未经处理的致病T细胞的技术。其次,目前的免疫抑制药物没有针对这些患者的正确免疫细胞。为了改善这些患者的治疗和生存,关键是要确定免疫系统在本病中所起的作用,确定目前的免疫抑制治疗对患者自身反应性免疫反应的影响,通过充分表征硬皮病的自身反应性免疫反应来确定新的治疗靶点,最后设计针对这些靶点的新的抑制剂。我们的特定假设是,直接从硬皮病患者身上分离的未经处理的自我反应性T细胞克隆可以用于识别新的治疗靶点和能够选择性结合这些致病细胞的小分子。这一假设基于以下观察结果。1)我们开发了一种从自身免疫患者中直接分离克隆扩增的纯T细胞群体的技术。2)通过组合筛选的方法,确定了活化T细胞亚群的高亲和力配体。3)筛选组合文库已确定T细胞活化所需的关键细胞内途径的抑制物。基于这些观察,这项建议的实验重点将是组合文库,以确定新的T细胞抑制小分子和T细胞特异性配体,试图开发一种高效的治疗方法,可以靶向并摧毁硬皮病和其他免疫介导性皮肤疾病中的致病T细胞。 与公共卫生相关:正常情况下,免疫系统的功能是抵御普通感冒等感染。在自身免疫的患者中,免疫系统的细胞会损害患者的组织和器官。一些自身免疫性疾病对免疫抑制治疗有反应,而另一些则非常难以治疗。硬皮病是一种自身免疫性疾病,治疗无效。我们将研究从硬皮病患者中分离出来的免疫细胞,并试图确定药物治疗的新靶点。

项目成果

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Emanual M. Maverakis其他文献

Emanual M. Maverakis的其他文献

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{{ truncateString('Emanual M. Maverakis', 18)}}的其他基金

Stratedigm S100EON high-parameter flow cytometer to support multi-institutional research programs
Stratigm S100EON 高参数流式细胞仪支持多机构研究项目
  • 批准号:
    10431674
  • 财政年份:
    2022
  • 资助金额:
    $ 230.88万
  • 项目类别:
Mentoring Translational Scientists in Clinical Trial Immune Monitoring
指导转化科学家进行临床试验免疫监测
  • 批准号:
    10359792
  • 财政年份:
    2021
  • 资助金额:
    $ 230.88万
  • 项目类别:
Mentoring Translational Scientists in Clinical Trial Immune Monitoring
指导转化科学家进行临床试验免疫监测
  • 批准号:
    10670051
  • 财政年份:
    2021
  • 资助金额:
    $ 230.88万
  • 项目类别:
Investigation and Development of New Therapeutic Avenues for Scleroderma
硬皮病新治疗途径的研究和开发
  • 批准号:
    8792820
  • 财政年份:
    2011
  • 资助金额:
    $ 230.88万
  • 项目类别:
Characterization of Pathogenic T cells in Alopecia Areata
斑秃致病性 T 细胞的特征
  • 批准号:
    8213547
  • 财政年份:
    2010
  • 资助金额:
    $ 230.88万
  • 项目类别:
Characterization of Pathogenic T cells in Alopecia Areata
斑秃致病性 T 细胞的特征
  • 批准号:
    7880365
  • 财政年份:
    2010
  • 资助金额:
    $ 230.88万
  • 项目类别:
Characterization of Pathogenic T cells in Alopecia Areata
斑秃致病性 T 细胞的特征
  • 批准号:
    8045448
  • 财政年份:
    2010
  • 资助金额:
    $ 230.88万
  • 项目类别:
gC399tr an inhibitor of autoimmunity
gC399tr 自身免疫抑制剂
  • 批准号:
    7476622
  • 财政年份:
    2008
  • 资助金额:
    $ 230.88万
  • 项目类别:
gC399tr an inhibitor of autoimmunity
gC399tr 自身免疫抑制剂
  • 批准号:
    7569013
  • 财政年份:
    2008
  • 资助金额:
    $ 230.88万
  • 项目类别:
gC399tr an inhibitor of autoimmunity
gC399tr 自身免疫抑制剂
  • 批准号:
    7779385
  • 财政年份:
    2008
  • 资助金额:
    $ 230.88万
  • 项目类别:

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