Natalizumab (Tysabri®) is a monoclonal antibody targeted at α4β1 integrin

Natalizumab is a selective adhesion-molecule inhibitor that binds to α4β1 integrin, which is present on all leukocytes, except neutrophils. It is thought to prevent migration of inflammatory cells into the brain in multiple sclerosis (MS). 

Mechanism of action

By binding to the α4β1 integrin, natalizumab blocks the interaction with its cognate receptor, vascular cell adhesion molecule-1 (VCAM-1), and ligands osteopontin, and an alternatively spliced domain of fibronectin, connecting segment-1 (CS-1). Natalizumab also blocks the interaction of α4β7 integrin with the mucosal addressin cell adhesion molecule-1 (MadCAM-1).

In MS, lesions are believed to be the consequence of activated T-lymphocytes that have crossed the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells and endothelial cells of the vessel wall. The disruption of molecular interactions by natalizumab prevents transmigration of mononuclear leukocytes across the endothelium into inflamed parenchymal tissue.  

Clinical use

In Europe, natalizumab is indicated for use in patients with highly active MS despite a full and adequate course of treatment with at least one disease modifying therapy, or in patients with rapidly evolving severe relapsing remitting MS defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI. Consult CHMP for details.

What can Sanquin do for you?

We have tests that:

- can measure the levels of free drug in the serum; levels of therapeutic antibodies are assessed using validated ELISAs.

- can measure the immunogenicity of natalizumab; human anti-human antibodies are quantified using validated antigen-binding tests (radioimmunoassay or RIA).

As we have hands-on experience in these assays, we can provide you with accurate and reproducible test results. 

Send in samples

If you want to use our drug level or ADA testing services, fill out this form and send it to us along with 1 ml frozen serum sample per patient.