natalizumab
Tysabri (natalizumab) is a monoclonal antibody from Biogen for highly active relapsing forms of multiple sclerosis and, in the United States, for moderately to severely active Crohn's disease after inadequate response to conventional therapy. It keeps inflammatory immune cells out of the brain and gut.
This page is based on FDA prescribing information and the EMA medicine record for natalizumab, cross-checked with DailyMed and the National Cancer Institute dictionary; the mechanism is explained in plain language, and analogies are used only where they stay accurate.
How it works
Explains what the medicine does in the body, not dosing, side effects, or safety.
An analogy
Immune cells circulating in the blood need a docking pass to exit into tissue such as the brain or gut. Alpha4 integrin is that pass: it locks onto VCAM-1 on the vessel wall and lets the cell through. Natalizumab covers the pass, so immune cells cannot dock and cross. With fewer inflammatory cells reaching the brain and intestine, the attacks that drive multiple sclerosis and Crohn's disease become less frequent.
In simple terms
Natalizumab is given by intravenous infusion and works on the traffic of immune cells rather than destroying them. Most white blood cells carry alpha4 integrin on their surface, which they use to stick to blood vessel walls and cross into tissue. Natalizumab binds alpha4 integrin and blocks that step, so fewer inflammatory cells enter the brain and spinal cord in multiple sclerosis, or the intestine in Crohn's disease. Because it also limits immune surveillance in the brain, treatment carries a risk of a rare brain infection called PML, which is why use is carefully monitored.
In depth
Natalizumab is a humanized recombinant IgG4 monoclonal antibody directed against the alpha4 subunit of the integrins alpha4beta1 (VLA-4) and alpha4beta7. By binding alpha4 integrin on leukocytes, it blocks alpha4-mediated adhesion to vascular cell adhesion molecule-1 (VCAM-1) on the endothelium, preventing transmigration of leukocytes into inflamed parenchymal tissue. In the central nervous system this limits recurrent inflammatory demyelination, and in the gut it reduces intestinal inflammation. The same restriction of immune surveillance underlies the increased risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab products, and expected benefit is weighed against this risk when initiating and continuing treatment.
See it in motion
A schematic animation of the mechanism — simplified for clarity, not drawn to scale.
Natalizumab covers the pass, so immune cells cannot dock and cross.
- Most white blood cells carry alpha4 integrin on their surface, which they use to stick to blood vessel walls and cross into tissue.
- Immune cells circulating in the blood need a docking pass to exit into tissue such as the brain or gut.
- Alpha4 integrin is that pass: it locks onto VCAM-1 on the vessel wall and lets the cell through.
- With fewer inflammatory cells reaching the brain and intestine, the attacks that drive multiple sclerosis and Crohn's disease become less frequent.
Target: Alpha4 integrin subunit (alpha4beta1 and alpha4beta7 integrins)
Adhesion molecules on most white blood cells; by binding VCAM-1 on blood vessel walls they let immune cells cross into tissue, so blocking the alpha4 subunit keeps inflammatory cells out of the brain and gut.
Approved uses
Approved uses differ by country and change over time. Always follow your local prescribing information.
Approved uses in United States
FDA- As monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
- For inducing and maintaining clinical response and remission in adults with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional Crohn's disease therapies and TNF-alpha inhibitors
Approved uses in European Union
EMA- As single disease-modifying therapy in adults with highly active relapsing-remitting multiple sclerosis, in patients with highly active disease despite a full and adequate course of treatment with at least one disease-modifying therapy, or in patients with rapidly evolving severe disease defined by two or more disabling relapses in one year together with one or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared with a recent MRI
Official sources
The statements on this page trace back to these records.
- Tysabri (natalizumab) — Summary of product characteristics and package leaflet, English version
European Medicines Agency
- DailyMed: TYSABRI (natalizumab) official US label
U.S. National Library of Medicine, DailyMed
- U.S. Food and Drug Administration: natalizumab prescribing information
U.S. Food and Drug Administration
- National Cancer Institute: natalizumab
National Cancer Institute
This page explains how the medicine works — it isn’t the patient leaflet. For anything that applies to you, read the leaflet that came with your medicine or ask your pharmacist.
MedUnfold provides educational content and is not medical advice. Always follow your local prescribing information and healthcare professional.