Therapeutic Strategy for Recurrent Spontaneous Abortion

复发性自然流产的治疗策略

• 批准号: 6999128
• 负责人: Darryl L. Carter
• 金额: $ 10万
• 依托单位: NORA, LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2006-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999128
• 关键词: Therapeutic; Strategy; Recurrent; Spontaneous; Abortion

DESCRIPTION (provided by applicant): Recurrent spontaneous abortion (RSA) is a serious medical condition that affects approximately 1-3% of reproductive age women. At present, there is no FDA approved treatment for RSA. We hypothesize that failure to suppress Th1 cytokine production early in pregnancy is a major cause of RSA. We hypothesize that recombinant human granulocyte colony stimulating factor (rhG-CSF) will prevent RSA caused by Th1 cytokine overproduction because rhG-CSF is known to cause an orchestrated shift from Th1 to Th2 cytokine predominance. Th2 cytokine predominance is associated with successful pregnancy outcome. In the current application, we propose to evaluate rhG-CSF as a treatment for RSA in a widely used mouse model of spontaneous abortion. Specifically, we plan to: 1. Test the hypothesis that rhG-CSF administered to CBA female mice at the time of conception will prevent spontaneous abortion. 2. To test the hypothesis that the protective effect of G-CSF against miscarriage is mediated by changes in the immune system as opposed to changes in the decidua and the placenta, where G-CSF and its receptor are normally expressed during pregnancy. Successful completion of the experiments described in this application will pave the way for a future human trial of rhG-CSF for the treatment of RSA.

描述（由申请人提供）：复发性自然流产（RSA）是一种严重的医学疾病，影响约1-3%的育龄妇女。目前，尚无FDA批准的RSA治疗方法。我们推测，未能抑制Th 1细胞因子的生产在怀孕早期是RSA的一个主要原因。我们假设，重组人粒细胞集落刺激因子（rhG-CSF）将防止RSA引起的Th 1细胞因子过度生产，因为rhG-CSF是已知的，导致精心策划的转变，从Th 1到Th 2细胞因子的优势。Th 2细胞因子优势与成功的妊娠结局相关。在目前的应用中，我们建议在广泛使用的自然流产小鼠模型中评估rhG-CSF作为RSA的治疗。具体而言，我们计划： 1.检验在受孕时给予CBA雌性小鼠rhG-CSF可预防自然流产的假设。 2.检验G-CSF对流产的保护作用是由免疫系统的变化介导的，而不是由蜕膜和胎盘的变化介导的假设，G-CSF及其受体在妊娠期间通常在蜕膜和胎盘中表达。 本申请中所述实验的成功完成将为rhG-CSF治疗RSA的未来人体试验铺平道路。