New, Fully Implantable Device for Selective Clearance of CSF-Target Molecules: Proof of Concept in a Murine Model of Alzheimer’s Disease
We have previously proposed a radical change in the current strategy to clear pathogenic proteins from the central nervous system (CNS) based on the cerebrospinal fluid (CSF)-sink 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. View Full-Text
I am a neurologist (at Hospital Universitario Central de Asturias, Oviedo) and professor of neurology (at Oviedo University) with research experience in clinical and translational neuroscience (at Oviedo University and at Instituto de Investigación Sanitaria del Principado de Asturias). I am focused on neurodegenerative diseases, from neuropsychology to neuroimaging and from neurogenetics to phenotypes. In the last years, I am particularly interested in understanding the molecular mechanisms of neurodegeneration: genes, and proteins; and in studying brain clearance systems and the molecular dynamics between cells, the interstitial fluid, and the cerebrospinal fluid. I am also interested in developing new systems for targeted drug delivery to the CNS.