Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise.
Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise.
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DOI：
10.1016/j.biopsych.2017.08.010
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发表时间：
2018-02-15
影响因子：
10.6
通讯作者：
van Dyck CH
中科院分区：
文献类型：
--
作者：
van Dyck CH
大多数公认的阿尔茨海默病的疾病改善治疗方法都是针对淀粉样蛋白-β（Aβ）肽的。在抗A β治疗方法中，发展最广泛的是免疫治疗特异性，通过给予外源性单克隆抗体（mAb）进行被动免疫。尽管单克隆抗体的测试充满了失败和令人困惑的结果，但从这些试验中获得的经验为更好的治疗提供了重要的线索。本文综述了迄今为止抗A β单克隆抗体进入阿尔茨海默病临床试验的经验，并检查了临床疗效的证据和安全性的主要问题，即，淀粉样蛋白相关的成像异常。由于mAb在其表位和它们识别的Aβ构象（单体、寡聚体、原纤维、原纤维）方面差异很大，因此还考虑了靶向不同物种的后果。抗A β mAb试验失败的一个经常被引用的解释是，它们在疾病过程中设置得太晚。新的试验确实正在评估前驱期和临床前阶段的治疗。我们应该期待看到更多的症状前阿尔茨海默病的研究加入正在进行的预防试验，其中单克隆抗体继续作为中流砥柱。
The majority of putative disease-modifying treatments in development for Alzheimer’s disease are directed against the amyloid-β (Aβ) peptide. Among the anti-Aβ therapeutic approaches, the most extensively developed is immunotherapy—specifically, passive immunization through administration of exogenous monoclonal antibodies (mAbs). Although testing of mAbs has been fraught with failure and confusing results, the experience gained from these trials has provided important clues for better treatments. This review summarizes the experience to date with anti-Aβ mAbs to enter clinical trials for Alzheimer’s disease and examines the evidence for clinical efficacy and the major problems with safety—i.e., amyloid-related imaging abnormalities. As mAbs differ considerably with regard to their epitopes and the conformations of Aβ that they recognize (monomers, oligomers, protofibrils, fibrils), the consequences of targeting different species are also considered. An often-cited explanation for the failure of anti-Aβ mAb trials is that they are set too late in the disease process. New trials are indeed evaluating treatments at prodromal and preclinical stages. We should expect to see additional studies of presymptomatic Alzheimer’s disease to join the ongoing prevention trials, for which mAbs continue to serve as the mainstay.
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DOI：
10.3233/jad-2011-110230
发表时间：
2011
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Kou J;Kim H;Pattanayak A;Song M;Lim JE;Taguchi H;Paul S;Cirrito JR;Ponnazhagan S;Fukuchi K
通讯作者：
Fukuchi K
影响因子：
4
作者：
Bohrmann, Bernd;Baumann, Karlheinz;Loetscher, Hansruedi
通讯作者：
Loetscher, Hansruedi
影响因子：
14
作者：
Farlow, Martin;Amold, Steven E.;Siemers, Eric R.
通讯作者：
Siemers, Eric R.
影响因子：
6
作者：
Bussière, T;Bard, F;Buttini, M
通讯作者：
Buttini, M
DOI：
10.1073/pnas.151261398
发表时间：
2001-07-17
影响因子：
11.1
作者：
DeMattos, RB;Bales, KR;Holtzman, DM
通讯作者：
Holtzman, DM