补体抑制剂在罕见病的临床应用

乐偲; 杜亚丽; 黄杨钰; 陈丽萌; 管宇宙; 韩冰

doi:10.12376/j.issn.2097-0501.2022.04.006

补体抑制剂在罕见病的临床应用

doi: 10.12376/j.issn.2097-0501.2022.04.006

1.
中国医学科学院北京协和医院肾内科，北京 100730
2.
中国医学科学院北京协和医院血液科，北京 100730
3.
中国医学科学院北京协和医院神经科，北京 100730

基金项目:

中国医学科学院医学与健康科技创新工程项目 2021-I2M-1-003

详细信息

通信作者:
韩冰, E-mail：hanbing_li@sina.com.cn

中图分类号: R453.9
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- 被引次数: 0
出版历程
- 收稿日期: 2022-05-13
- 录用日期: 2022-07-05
- 网络出版日期: 2022-12-23

Complement Inhibitors in Rare Diseases

1.
Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
3.
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funding:

CAMS Innovation Fund for Medical Sciences 2021-I2M-1-003

More Information

Corresponding author: HAN Bing, E-mail: hanbing_li@sina.com.cn

摘要

摘要: 补体系统是人体的一种自我保护机制，补体系统的异常活化参与多种疾病的发生、发展。补体抑制剂的使用为很多罕见疾病，如阵发性睡眠性血红蛋白尿症(PNH)、非典型溶血尿毒综合征(aHUS)等，带来了里程碑式的进步。近年来，补体抑制剂的应用也逐渐向其他补体相关疾病领域拓展。本文结合近年文献，就补体抑制剂在较为成熟的罕见病领域的应用进行总结，也对其今后在相关罕见病领域的应用前景予以展望。
- 补体抑制剂 /
- 阵发性睡眠性血红蛋白尿症 /
- 非典型溶血尿毒综合征 /
- 重症肌无力
Abstract: The complement system is a self-protection mechanism of the human body. The abnormal activation of the complement system is involved in the occurrence and development of various diseases. The application of complement inhibitors in many rare diseases was a milestone in leading to the progress of such disease as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and others. Recently, the application of complement inhibitors has gradually expanded to other complement-related diseases. This review summarizes the literature on the current application of complement inhibitors in rare diseases and looks into the prospects of the application in the rare diseases.
- complement inhibitors /
- paroxysmal nocturnal hemoglobinuria /
- atypical hemolytic uremic syndrome /
- myasthenia gravis
注释:

作者贡献：乐偲、杜亚丽、黄杨钰负责文稿起草；陈丽萌、管宇宙、韩冰负责文稿构思、设计及批判性审阅；韩冰负责文稿总体策划、指导及研究经费获取。

利益冲突：所有作者均声明不存在利益冲突。

HTML全文

图 1 补体活化途径及治疗靶点

C4BP: C4结合蛋白；CFB: 补体因子B；CFD: 补体因子D；CFH: 补体因子H；CFI: 补体因子I；CR: 补体受体；MBL: 甘露聚糖结合凝集素；MASP: 甘露聚糖结合凝集素相关丝氨酸蛋白酶; Eculizumab: 依库珠单抗

Figure 1. Complement activation pathways and drug targets

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表 1 目前上市或正在进行临床试验的部分补体抑制剂

Table 1. Complement inhibitors that are approved or in clinical trials for rare diseases

补体抑制剂名称及类型	阵发性睡眠性血红蛋白尿症(PNH)	非典型溶血尿毒综合征(aHUS)	C3肾小球病	重症肌无力(MG)
依库珠单抗(C5)	FDA获批上市，中国指南推荐用于PNH治疗	FDA获批上市，中国指南推荐用于aHUS治疗	个案报道	获批
Ravulizumab (C5)	获批上市	Ⅲ期		Ⅲ期
Crovalimab (C5)	Ⅲ期	Ⅲ期
SB12 (C5)	Ⅲ期
CAN106(C5)	Ⅰ期
Pozelimab+Cemdisiran (C5)				Ⅰ，Ⅲ期
Zilucoplan (C5)				Ⅱ，Ⅲ期
Pegcetacoplan(APL-2，C3)	获批上市
CG001(C3)	Ⅰ期
Iptacopan(LNP023，B因子)	Ⅲ期	Ⅲ期	Ⅲ期
Danicopan (D因子)	获批上市		Ⅱ期
BCX9930(D因子)	Ⅲ期
ALXN 2050 (D因子)				Ⅱ期

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