通过肺部输送的Anticalin Jagged-1抗剂减少了实验性气道粘液过度生成和阻塞
Katharina Heinzelmann1, Athanasios Fysikopoulos1, Thomas J Jaquin1
1Pieris Pharmaceuticals GmbH, Hallbergmoos, Germany.
概括
在临床前模型中,新型可吸入的Jagged-1抗剂有效地减少了气道粘液的过度生产和阻塞. 这种有针对性的方法为慢性肺部疾病提供了潜在的治疗益处,同时最大限度地减少了全身副作用.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 粘液过分和阻塞是慢性肺部疾病的关键特征,影响严重程度和死亡率.
- 格-1/诺奇通路调节气道分泌和状细胞分化,呈现出治疗点.
- 对Notch通路的系统向具有风险,因为它在多个器官中的作用.
研究的目的:
- 开发和评估肺部输送的Jagged-1抗剂,用于治疗肺部疾病中的粘液过量产生和阻塞.
- 在ex vivo和in vivo模型中评估基于Anticalin的Jagged-1抗剂的疗效.
主要方法:
- 使用Anticalin技术设计了强效和选择性可吸入的Jagged-1对手.
- 研究了通过炎症性细胞因子刺激的初级气道细胞培养物的ex vivo影响.
- 在IL-13和室内灰尘虫过敏原挑战的小鼠和囊性纤维化/COPD转基因小鼠模型中评估了体内疗效.
主要成果:
- 在细胞培养中,Jagged-1抗卡林结合蛋白降低了粘素基因表达和粘膜细胞代谢.
- 在小鼠模型中,肺部输送减少了粘膜细胞代谢,上皮质加厚和粘液过度生产.
- 活体模型显示粘液阻塞特征减少,粘液细胞减少,纤毛细胞增加.
结论:
- 肺部输送的Jagged-1抗体显示出粘膜阻塞性肺部疾病的治疗潜力.
- 吸入是一种可行的策略,用于准Jagged-1/Notch通道,以减少气道粘液.
- 这些发现支持Jagged-1抗剂作为一种有前途的治疗粘液相关的肺病理.
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