Departamento de Biología Funcional, Área de Fisiología, Universidad de Oviedo, 33006 Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias, 33011 Oviedo, Spain.
Int J Mol Sci. 2022 Aug 17;23(16):9256. doi: 10.3390/ijms23169256.
We have previously proposed a radical change in the current strategy to clear pathogenic proteins from the central nervous system (CNS) based on the therapeutic strategy, whereby pathogenic proteins can be removed directly from the CNS via CSF. To this aim, we designed and manufactured an implantable device for selective and continuous apheresis of CSF enabling, in combination with anti-amyloid-beta (Aβ) monoclonal antibodies (mAb), the clearance of Aβ from the CSF. Here, we provide the first proof of concept in the APP/PS1 mouse model of Alzheimer's disease (AD). Devices were implanted in twenty-four mice (seventeen APP/PS1 and seven Wt) with low rates of complications. We confirmed that the apheresis module is permeable to the Aβ peptide and impermeable to mAb. Moreover, our results showed that continuous clearance of soluble Aβ from the CSF for a few weeks decreases cortical Aβ plaques. Thus, we conclude that this intervention is feasible and may provide important advantages in terms of safety and efficacy.
我们之前提出了一种激进的改变，即基于治疗策略，从中枢神经系统（CNS）中清除致病蛋白，从而可以直接从 CNS 通过 CSF 清除致病蛋白。为此，我们设计并制造了一种可植入的设备，用于选择性和连续的 CSF 清除，结合抗淀粉样蛋白-β（Aβ）单克隆抗体（mAb），可以从 CSF 中清除 Aβ。在这里，我们在阿尔茨海默病（AD）的 APP/PS1 小鼠模型中提供了第一个概念验证。将设备植入 24 只小鼠（17 只 APP/PS1 和 7 只 Wt）中，并发症发生率低。我们证实了清除模块对 Aβ 肽是可渗透的，对 mAb 是不可渗透的。此外，我们的结果表明，连续清除 CSF 中的可溶性 Aβ 数周可减少皮质 Aβ 斑块。因此，我们得出结论，这种干预是可行的，并且在安全性和疗效方面可能具有重要优势。
