The renaissance of complement therapeutics.
The renaissance of complement therapeutics.
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DOI：
10.1038/nrneph.2017.156
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Lambris JD
中科院分区：
文献类型：
--
作者：
Ricklin D;Mastellos DC;Reis ES;Lambris JD
越来越多的临床病症涉及补体系统的病理贡献-其中许多影响肾脏-已经刺激了对调节该宿主防御途径的治疗选择的重新兴趣。分子洞察力，技术进步和补体特异性药物依库珠单抗的第一个十年临床经验，有助于对治疗性补体抑制的信心不断增长。目前正在临床试验中评估20多种针对补体级联反应各个阶段的候选药物，其他药物正在临床前开发中。鉴于补体在广泛的临床病症中的复杂和独特的参与，包括罕见的肾脏疾病、移植排斥和血液透析诱导的炎症，显然需要这种多样性。现有的药物不能应用于所有补体驱动的疾病，每种适应症都必须单独评估。除了考虑最佳干预点和经济因素外，患者分层对于确定每个患者的最佳补体特异性治疗至关重要。本综述概述了治疗概念，靶点和候选药物，总结了临床试验的见解，并反映了肾脏疾病及其他疾病的补充疗法开发的现有挑战。
The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond.
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影响因子：
6.2
作者：
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通讯作者：
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DOI：
10.1002/path.4635
发表时间：
2016-01
期刊：
The Journal of pathology
影响因子：
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作者：
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DOI：
10.2215/cjn.12901211
发表时间：
2012-05-01
影响因子：
9.8
作者：
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通讯作者：
Appel, Gerald B.