基于系统免疫学的药物重新定位框架,以向动脉样硬化的炎症
Letizia Amadori1,2, Claudia Calcagno3, Dawn M Fernandez4
1Department of Medicine, Division of Cardiology, NYU Cardiovascular Research Center, New York, NY, USA.
Nature cardiovascular research
|September 29, 2023
概括
对动脉样硬化心血管疾病 (ASCVD) 需要新的免疫疗法. 这项研究重新定位了药物的用途,在临床前模型中确定了萨拉卡提尼布作为一种潜在的治疗方法,通过逆转炎症和减少动脉样硬化进展.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 药物发现 药物发现 药物发现
背景情况:
- 动脉样硬化心血管疾病 (ASCVD) 是由炎症机制驱动的,需要新的免疫疗法.
- 目前针对ASCVD的治疗策略缺乏有针对性的免疫调节方法.
研究的目的:
- 为确定ASCVD的免疫疗法制定药物重用策略.
- 在动脉样硬化的临床前模型中验证潜在的候选药物.
主要方法:
- 集成的飞行时间质量细胞计和RNA测序,以识别ASCVD特定的炎症特征.
- 利用LINCS L1000数据集来识别能够逆转这些特征的药物.
- 在老鼠和子模型中进行了ex vivo药物查和临床前研究.
主要成果:
- 在ASCVD患者样本中确定了独特的炎症特征.
- 萨拉卡提尼布是一种SRC和ABL抑制剂,可以逆转ASCVD相关的炎症.
- 萨拉卡提尼布通过调节巨细胞表型,减少了Apoe-/-小鼠的动脉样硬化进展.
- 在子动脉硬化模型中,萨拉卡提尼布降低了斑块炎症.
结论:
- 以系统免疫学为驱动的方法可以促进心血管免疫疗法的药物重用.
- 萨拉卡提尼布通过向炎症途径,显示出作为ASCVD治疗剂的潜力.
- 临床前验证支持萨拉卡提尼布用于治疗动脉样硬化心血管疾病的开发.
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