血管类3抑制和肝脏:更少就是更多?
Reindert F Oostveen1, G Kees Hovingh, Erik S G Stroes
1Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Current opinion in lipidology
|October 11, 2023
概括
抑制ANGPTL3显示出降低脂蛋白的前景,但存在安全问题. 在vupanorsen和ARO-ANG3之间异常的肝脂肪结果突出显示,需要在ANGPTL3疗法中仔细监测安全性.
科学领域:
- 心血管药理学心血管药理学
- 肝病学 肝病学是一种肝病学.
- 遗传医学是一种遗传医学.
背景情况:
- 血管类3 (ANGPTL3) 抑制是减少apoB-lipoproteins的治疗标.
- 最近的ANGPTL3抑制研究中出现了相互矛盾的肝脏安全数据.
研究的目的:
- 讨论在ANGPTL3抑制研究中对抗肝脏安全结果的潜在机制和影响.
- 为了分析vupanorsen (反感) 和ARO-ANG3 (siRNA) 之间关于肝脏影响的差异.
主要方法:
- 对ANGPTL3抑制剂vupanorsen和ARO-ANG3.3的最近临床试验数据的审查.
- 分析报告的肝转氨酶水平和肝脂肪分数的变化.
- 探索不同安全配置文件的潜在机制.
主要成果:
- 由于肝转氨酶的增加和剂量依赖性肝脂肪的增加 (高达75%),Vupanorsen (抗感) 的发展停止了.
- ARO-ANG3 (siRNA) 显示了剂量依赖性肝脂肪减少的初步证据 (高达30%).
结论:
- 差异可能源于不同水平的目标抑制或特定于该分子或平台的非目标效应.
- 强大的ANGPTL3抑制策略需要严格的肝脏安全性评估.
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