Tau passive immunotherapy in mutant P301L mice: antibody affinity versus specificity.
Tau passive immunotherapy in mutant P301L mice: antibody affinity versus specificity.
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DOI：
10.1371/journal.pone.0062402
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Davies P
中科院分区：
文献类型：
--
作者：
d'Abramo C;Acker CM;Jimenez HT;Davies P
在过去的十年里，利用抗体治疗神经退行性疾病得到了迅速的发展。到目前为止，阿尔茨海默病的免疫治疗方法主要针对淀粉样β蛋白，因为它是一种分泌蛋白，可以在血浆和脑脊液中找到，因此可以被循环中的抗体获得。最近很少有文献提出用抗tau的单抗治疗tau病。我们的实验室已经开始利用突变的P301L小鼠对不同类别的tau单抗进行系统研究。以每周10 mg/kg的剂量接种3月龄和7月龄突变tau小鼠，直至分别达到7月龄和10月龄。我们的数据有力地支持了这样的观点，即在P301L动物中，用针对PHF-tau的构象单抗MC1治疗后，tau病理的发展速度有效地降低，而注射高亲和力tau序列抗体DA31则没有发挥这种好处。MC1的总体疗效优于DA31，提示在治疗应用中，特异性比亲和力更重要。不幸的是，P301L处理的小鼠的存活率在用MC1或PHF1免疫时并没有提高，PHF1是一种高亲和力的磷酸tau抗体，以前报道过可以有效地减少病理性tau。这些数据表明，在突变的tau模型中进行被动免疫治疗可能在减少tau病变的发展方面是有效的，但仍有大量的工作要做，以仔细选择tau表位作为靶点。
The use of antibodies to treat neurodegenerative diseases has undergone rapid development in the past decade. To date, immunotherapeutic approaches to Alzheimer’s disease have mostly targeted amyloid beta as it is a secreted protein that can be found in plasma and CSF and is consequently accessible to circulating antibodies. Few recent publications have suggested the utility of treatment of tau pathology with monoclonal antibodies to tau. Our laboratory has begun a systematic study of different classes of tau monoclonal antibodies using mutant P301L mice. Three or seven months old mutant tau mice were inoculated weekly with tau monoclonal antibodies at a dose of 10 mg/Kg, until seven or ten months of age were reached respectively. Our data strongly support the notion that in P301L animals treated with MC1, a conformational monoclonal antibody specific for PHF-tau, the rate of development of tau pathology is effectively reduced, while injecting DA31, a high affinity tau sequence antibody, does not exert such benefit. MC1 appears superior to DA31 in overall effects, suggesting that specificity is more important than affinity in therapeutic applications. Unfortunately the survival rate of the P301L treated mice was not improved when immunizing either with MC1 or PHF1, a high affinity phospho-tau antibody previously reported to be efficacious in reducing pathological tau. These data demonstrate that passive immunotherapy in mutant tau models may be efficacious in reducing the development of tau pathology, but a great deal of work remains to be done to carefully select the tau epitopes to target.
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tau 病理学 htau 小鼠模型中认知和突触功能的年龄依赖性损害。
影响因子：
5.3
作者：
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影响因子：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
Davies, P