Manuel Menéndez: Targeting soluble Abeta oligomers in the CSF via intrathecal pseudodelivery

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 occurs 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.

Simulated dynamics of amyloid clearance using intravenous (IV) and intrathecal pseudodelivery of monoclonal antibodies (mAbs). Intrathecal pseudodelivery achieves rapid reduction of soluble Aβ in cerebrospinal fluid (CSF), leading to amyloid PET negativity by month 132. In contrast, intravenous administration reduces soluble Aβ more gradually, achieving PET negativity by month 150.

My affiliation and interests

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 exploring the 360º panoramic of neurodegenerative diseases: from neuropsychology to neuroimaging and from neurogenetics to phenotypes. In the last few years, I have been particularly interested in understanding the molecular mechanisms of neurodegeneration: genes, RNA, 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.

Liquorpheresis

Liquorpheresis, also known as cerebrospinal fluid (CSF) exchange, CSF filtration, or CSF apheresis, is a medical procedure designed to remove and replace cerebrospinal fluid. This technique treats certain neurological conditions by filtering out harmful substances or altering the composition of the CSF.

Key Points:

Procedure: During liquorpheresis, CSF is withdrawn from the patient and processed through a device that removes specific components (such as antibodies, immune complexes, or toxins). The filtered CSF or a substitute fluid is then returned to the intrathecal space.
Indications: Liquorpheresis is primarily used for conditions where harmful substances in the CSF need to be removed or reduced. These conditions might include certain autoimmune diseases, infections, or neuroinflammatory disorders.
Benefits: By directly modifying the CSF, liquorpheresis can rapidly reduce the concentration of pathological substances, potentially leading to quicker symptom relief and improved outcomes in conditions where these substances play a critical role.
Risks and Considerations: As with any invasive procedure, risks include infection, bleeding, and potential complications from the fluid exchange. The benefits must be weighed against these risks on a case-by-case basis.

Clinical Applications:

Liquorpheresis is still a relatively specialized and less common procedure compared to other apheresis techniques. However, it holds the potential for treating a range of neurological disorders, particularly those involving pathogenic factors within the CSF.

In summary, liquorpheresis is a procedure that involves removing and replacing cerebrospinal fluid to treat neurological conditions. It filters out harmful substances and potentially improves patient outcomes.

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Targeting soluble Abeta oligomers in the CSF via intrathecal pseudodelivery

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