Granulocyte Colony Stimulating Factor Treatment For Croh

粒细胞集落刺激因子治疗克罗氏病

• 批准号: 6987028
• 负责人: Peter Mannon
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6987028
• 关键词: Crohn' s disease; cellular immunity; clinical trials; colony stimulating factor; cytokine; drug administration rate /duration; endoscopy; enzyme linked immunosorbent assay; flow cytometry; gastrointestinal disorder chemotherapy; gastrointestinal imaging /visualization; gene expression; helper T lymphocyte; human genetic material tag; human subject; human therapy evaluation; immunogenetics; immunomodulators; immunoregulation; immunotherapy; patient oriented research; tissue /cell culture

This open-label trial of G-CSF in Crohn's disease seeks to establish the safety and study the efficacy of this drug to induce remission in moderately active disease. We have screened 23 and enrolled 12 subjects in this protocol to date. Responses have ranged from complete remission to no response at all. We are accruing data on changes in cytokine secretion by peripheral and lamina propria mononuclear cells and dendritic cell populations. We are correlating these with clinical parameters including biochemical markers of gut inflammation. The higher dose cohort has now begun enrollment and oour plans are to double the treatment period based upon our current data of response dependent on duration of induced changes in dendritic cell populations. The major scientific advance has been the correlation of induction of Th2 and regulatory cytokines with clinical improvement in patients with active Crohn's disease. G-CSF represents a novel approach to Crohn's disease therapy as a true immunomodulator rather than immunosuppressant or blocker of inflammatory mediators. This advance fills a gap in the knowledge of how the mucosal cytokine milieu can affect the clinical expression of Crohn's disease. In addition this advance directs future research to look at other candidate therapeutic targets involved in the G-CSF response, provides a basis for characterizing a patient phenotype which correlates with novel disease susceptibility genes, and provides a rational for integrating this therapy with other complementary agents and for use in maintaining disease remission.

这项G-CSF在克罗恩病中的开放标签试验旨在确定该药物在中度活动性疾病中诱导缓解的安全性和有效性。迄今为止，我们已筛选了23例受试者，并在本方案中入组了12例受试者。反应范围从完全缓解到完全无反应。我们正在积累外周血和固有层单核细胞和树突状细胞群细胞因子分泌变化的数据。我们正在将这些与临床参数（包括肠道炎症的生化标志物）相关联。高剂量队列现已开始入组，我们的计划是根据我们目前的数据，根据树突状细胞群诱导变化的持续时间，将治疗期延长一倍。 主要的科学进展是诱导Th 2和调节细胞因子与活动性克罗恩病患者临床改善的相关性。G-CSF作为一种真正的免疫调节剂而不是免疫抑制剂或炎症介质阻断剂，代表了克罗恩病治疗的新方法。这一进展填补了关于粘膜细胞因子环境如何影响克罗恩病临床表现的知识空白。此外，这一进展指导未来的研究，以寻找其他候选治疗目标参与G-CSF反应，提供了一个基础，表征患者的表型与新的疾病易感基因相关，并提供了一个合理的整合这种疗法与其他互补剂，并用于维持疾病缓解。