Allergy Asthma Proc. 2020 Nov 1;41(Suppl 1):S51-S54. doi: 10.2500/aap.2020.41.200056.
The future therapies for hereditary angioedema will likely involve the development of oral agents as alternatives to parenteral administration of drugs, specific targeting of proteins and/or enzymes that are not yet possible (e.g., factor XIIa), new agents that target the β₂ receptor with sustained action properties, testing of products to determine whether the β receptor contributes significantly to attacks of angioedema, disrupting protein synthesis by using RNA technology as an alternative to enzyme inhibition, and, finally, gene therapy to attempt to cure the disease. Complete inhibition of attacks may well require sustained blood levels of C1 inhibitor that exceed 85% of normal, and it may be possible to delete the prekallikrein gene (analogous to familial prekallikrein deficiency), which is the one factor that might alleviate bradykinin formation, even by factor XII-independent initiating mechanisms, with the possible exception of Mannose Associated Serine Protease 1 (MASP-1) cleavage of high molecular weight kininogen (HK). Deletion of the light chain of high-molecular-weight kininogen would eliminate all possibilities for bradykinin formation, except tissue kallikrein cleavage of low-molecular-weight kininogen to support normal physiologic function to at least 50%.
遗传性血管性水肿的未来治疗方法可能包括开发口服药物作为替代静脉注射药物的方法，针对目前尚无法靶向的蛋白质和/或酶（例如因子 XIIa）进行特定靶向治疗，开发具有持续作用特性的靶向β₂受体的新型药物，测试产品以确定β受体是否对血管性水肿发作有重大影响，利用 RNA 技术抑制蛋白质合成作为酶抑制的替代方法，最后，尝试基因治疗以治愈该疾病。完全抑制发作可能需要持续的血液 C1 抑制剂水平超过正常水平的 85%，并且可能可以删除前激肽释放酶基因（类似于家族性前激肽释放酶缺乏症），这是一种可能减轻缓激肽形成的因素，即使通过因子 XII 非依赖性起始机制也是如此，除了甘露糖相关丝氨酸蛋白酶 1（MASP-1）对高分子量激肽原（HK）的切割之外。删除高分子量激肽原的轻链将消除形成缓激肽的所有可能性，除非组织激肽酶对低分子量激肽原的切割以支持正常生理功能至少达到 50%。
