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Review Article

基于 PCSK9 抑制的治疗方法：免疫疗法-观点

卷 29, 期 6, 2022

发表于: 12 January, 2022

页: [980 - 999] 页: 20

弟呕挨: 10.2174/0929867328666211027125245

价格: $65

摘要

前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 抑制剂 (PCSK9-I) 是降低心血管风险的新型治疗工具。这些药物通过降低对他汀类药物耐药/不耐受的高胆固醇血症患者的低密度脂蛋白胆固醇 (LDL-C) 起作用。目前临床批准和研究的 PCSK9-I 通常通过阻断血浆中的 PCSK9 活性或抑制其表达或肝细胞分泌来发挥作用。研究最广泛的方法是通过完全人源化单克隆抗体 (mAb)、evolocumab 和 alirocumab 破坏 PCSK9/LDL 受体 (LDLR) 相互作用，这些抗体已被批准用于治疗高胆固醇血症和动脉粥样硬化性心血管疾病 (CVD)。此外，一种称为 inclisiran 的小干扰 RNA 可特异性抑制肝细胞中 PCSK9 的表达，与 mAb 一样有效，但每年给药两次。由于这种治疗方法的高成本，已经对其他几种 PCSK9-I 进行了调查，包括基于肽的抗 PCSK9 疫苗和口服抗 PCSK9 小分子，它们正在临床前和 I 期临床研究中进行研究。有趣的是，与 mAb PCSK9-I 相比，抗 PCSK9 疫苗接种被认为是一种更广泛可行和更具成本效益的治疗工具，用于管理高胆固醇血症。本综述将讨论 PCSK9-I 在临床前和临床研究中的降低 LDL 和心脏保护作用，主要是基于免疫治疗的抑制剂，包括 mAb 和疫苗。

关键词: Alirocumab、evolocumab、免疫疗法、inclisiran、PCSK9、疫苗

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