Repurposing CRH antagonists for the treatment of endometriosis

重新利用 CRH 拮抗剂治疗子宫内膜异位症

基本信息

  • 批准号:
    10746682
  • 负责人:
  • 金额:
    $ 7.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-01 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Endometriosis is a chronic condition that affects 10% of reproductive-aged women worldwide. Unfortunately, up to 59% of women with endometriosis do not respond to the available treatments and continue to suffer from endometriosis-associated pain or recurrent pain after treatment cessation. Therefore, treatment alternatives that deviate from the current therapeutic focus are urgently needed. The corticotrophin-releasing hormone receptor type 1 (CRHR1) is a largely unexplored target. Corticotropin-releasing hormone (CRH), which activates the CRHR1, is a critical molecule in the hypothalamic-pituitary-adrenal (HPA) axis that integrates stress and endocrine responses both in the brain and in peripheral tissues. CRHR1 is abundant in the endometrium and ovaries and has a role in developing endometriotic tissues, as demonstrated by the team's previous work. CRHR1 antagonists were introduced into clinical trials for mood and gastrointestinal disorders with little to no effect on those diseases and have never reached approval for commercial use. Previous work from the research team demonstrated that short-term treatment with antalarmin, a CRHR1 antagonist frequently used in pre-clinical experimentation, showed a 30% decrease in endometriosis development and a 60% decrease in the weight and size of endometriosis vesicles. In continuation of these efforts, the overarching goal is to develop and commercialize CRHR1 antagonists to treat endometriosis. The research team will focus on a compound recently out of patent and reached Phase 2 clinical trials but was not effective for depression, anxiety, or alcoholism. To begin addressing our goal, two specific aims were designed: on Aim 1, we will determine the effectiveness of a clinically relevant CRHR1 antagonist for endometriosis treatment, including its effectiveness in decreasing associated pain. Aim 2 will determine whether the CRHR1 antagonist affects the gonadal axis's cyclic hormonal activity, independent of antiproliferative activity. Both aims will be done using the well-established autotransplantation rat model of endometriosis, allowing for effective quantification and characterization of endometriotic vesicles. Completed aims will reveal the optimal intervention for halting endometriosis progression and predict possible mechanisms of action directly associated with the role of CRHR1 in the gonadal system. Future efforts will focus on how the CRHR1 antagonism impacts fertility and fecundity, which are critical factors to apply for re-introduction into clinical testing at the FDA. Bringing CRHR1 antagonists into the commercial field have the strong potential of decreasing surgical interventions in women with endometriosis, resulting in thousands of dollars saved in healthcare and indirect costs. The research team has identified the potential to repurpose CRHR1 antagonists, but before being re-introduced into clinical trials, additional proof of action and pre-clinical effectiveness is needed.
项目总结

项目成果

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Caroline B Appleyard其他文献

Caroline B Appleyard的其他文献

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{{ truncateString('Caroline B Appleyard', 18)}}的其他基金

The Enteric Glia as a Possible Target for Symptom Relief in Endometriosis
肠胶质细胞作为缓解子宫内膜异位症症状的可能目标
  • 批准号:
    10625609
  • 财政年份:
    2023
  • 资助金额:
    $ 7.12万
  • 项目类别:
Repurposing CRH antagonists for the treatment of endometriosis
重新利用 CRH 拮抗剂治疗子宫内膜异位症
  • 批准号:
    10602801
  • 财政年份:
    2022
  • 资助金额:
    $ 7.12万
  • 项目类别:
G-RISE at Ponce Health Sciences University
庞塞健康科学大学的 G-RISE
  • 批准号:
    10360344
  • 财政年份:
    2022
  • 资助金额:
    $ 7.12万
  • 项目类别:
G-RISE at Ponce Health Sciences University
庞塞健康科学大学的 G-RISE
  • 批准号:
    10610838
  • 财政年份:
    2022
  • 资助金额:
    $ 7.12万
  • 项目类别:
Training and Career Development
培训和职业发展
  • 批准号:
    8464860
  • 财政年份:
    2012
  • 资助金额:
    $ 7.12万
  • 项目类别:
Stress: Potential Impact on an Animal Model of Endometriosis
压力:对子宫内膜异位症动物模型的潜在影响
  • 批准号:
    8468876
  • 财政年份:
    2012
  • 资助金额:
    $ 7.12万
  • 项目类别:
Research Education Core
研究教育核心
  • 批准号:
    10249958
  • 财政年份:
    2012
  • 资助金额:
    $ 7.12万
  • 项目类别:
Research Education Core
研究教育核心
  • 批准号:
    10761658
  • 财政年份:
    2012
  • 资助金额:
    $ 7.12万
  • 项目类别:
THE ROLE OF BACTERIAL PEPTIDES IN CHRONIC INTESTINAL INFLAMMATION
细菌肽在慢性肠道炎症中的作用
  • 批准号:
    8357063
  • 财政年份:
    2011
  • 资助金额:
    $ 7.12万
  • 项目类别:
Stress: Potential Impact on an Animal Model of Endometriosis
压力:对子宫内膜异位症动物模型的潜在影响
  • 批准号:
    8180413
  • 财政年份:
    2011
  • 资助金额:
    $ 7.12万
  • 项目类别:

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