Intrathecal Immunoselective Nanopheresis for Alzheimer's Disease: What and How? Why and When?

Abstract

Nanotechnology is transforming therapeutics for brain disorders, especially in developing drug delivery systems. Intrathecal immunoselective nanopheresis with soluble monoclonal antibodies represents an innovative approach in the realm of drug delivery systems for Central Nervous System conditions, especially for targeting soluble beta-amyloid in Alzheimer's disease. This review delves into the concept of intrathecal immunoselective nanopheresis. It provides an overall description of devices to perform this technique while discussing the nanotechnology behind its mechanism of action, its potential advantages, and clinical implications. By exploring current research and advancements, we aim to provide a comprehensive understanding of this novel method, addressing the critical questions of what it is, how it works, why it is needed, and when it should be applied. Special attention is given to patient selection and the optimal timing for therapy initiation in Alzheimer's, coinciding with the peak accumulation of amyloid oligomers in the early stages. Potential limitations and alternative targets beyond beta-amyloid and future perspectives for immunoselective nanopheresis are also described.

Keywords: Alzheimer’s disease; amyloid-oligomers; drug delivery systems; immunoselective nanopheresis; intrathecal delivery; monoclonal antibodies; nanoporous membranes; neurodegenerative diseases.

Figure 1

Conceptual illustration of intrathecal immunoselective nanopheresis. This figure depicts the use of nanoporous membranes in combination with soluble mAbs to selectively filter target low size molecules from the CSF. Immunoselective nanopheresis can both be considered a type of drug pseudodelivery, where the compounds are monoclonal antibodies that provide the target-selectivity (on the left); and a way to achieve CSF filtration (liquorpheresis) (on the right).

Figure 2

Key components in an intrathecal immunoselective nanopheresis device for soluble mAbs: the intrathecal catheter and the subcutaneous reservoir with a port for percutaneous access and a capsule with nanoporous membranes for selective molecular permeability.

Figure 3

Hypothetical changes in Aβ oligomers during disease progression are transferred to the model of AD biomarker changes, according to Jack et al. A peak in sAβOs takes place in the early symptomatic or presymptomatic stage. Apolipoprotein E (APOE) gene ε4 allele carriers show higher oligomer concentrations, with a peak at a more advanced disease stage, but still in the early stages of the disease. Image from Blomeke [36], modified after Jack et al. [74].