Natalizumab and PML in MS

Anthony T Reder MD (Dr. Reder of the University of Chicago served on advisory boards and as a consultant for Bayer, Biogen Idec, Caremark Rx, Genentech, Genzyme, Novartis, Questcor/Malinkrodt, Serono, and Teva-Marion.)
Raymond P Roos MD, editor. (Dr. Roos of the University of Chicago owns stock in Amgen, Express Scripts, Isis, and Merck.)
Originally released August 2, 2005; last updated July 22, 2016; expires July 22, 2019

This article includes discussion of natalizumab and PML in MS and natalizumab and progressive multifocal leukoencephalopathy in multiple sclerosis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

White blood cells use adhesion molecules to attach to CNS endothelial cells, then penetrate the blood-brain barrier, and then cause inflammatory demyelination in multiple sclerosis. Antibodies to the VLA-4 adhesion molecule (natalizumab) prevent exacerbations and progression of multiple sclerosis. Some patients on this therapy have developed progressive multifocal leukoencephalopathy (PML). The author discusses the role of adhesion molecules in immune activation, penetration of the blood-brain barrier, and provocation and prevention of PML. The most recent information on monitoring for PML and clear definitions of the risk of PML are detailed.

Key points

 

• Natalizumab binds to very late activation antigen-4 (VLA-4) on immune cells. These cells no longer bind to CNS endothelium and can't cross the blood-brain barrier.

 

• The drug lowers the number of CSF T cells by at least 10-fold.

 

• With less immune surveillance in the brain, and perhaps actual activation of the virus by the treatment, the ordinarily innocuous JC virus can cause progressive multifocal leukoencephalopathy (PML).

 

• New assays that quantitate serum antibodies to JC virus allow better estimation of risk for PML.

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