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Published online before print April 7, 2005, doi:10.1212/01.WNL.0000158329.30470.D0)
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 Volume 64, Number 8, April 26, 2005
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NEUROLOGY 2005;64:1336-1342
© 2005 American Academy of Neurology
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Anti-{alpha}4 integrin therapy for multiple sclerosis

Mechanisms and rationale

George P.A. Rice, MD, Hans-Peter Hartung, MD and Peter A. Calabresi, MD

From the Department of Clinical Neurological Sciences (Dr. Rice), University of Western Ontario, London Health Sciences Centre, Canada; Department of Neurology (Dr. Hartung), Heinrich-Heine University, Duesseldorf, Germany; and Department of Neurology (Dr. Calabresi), The Johns Hopkins Hospital, Baltimore, MD.

Address correspondence and reprint requests to Dr. George P.A. Rice, Department of Clinical Neurologic Sciences, University of Western Ontario, London Health Sciences Centre, University Campus, 339 Windermere Road, London, Ontario, Canada N6A 5A5; e-mail: grice{at}uwo.ca

The symptoms, severity, and course of multiple sclerosis (MS) vary among patients, leading to complex treatment issues. In recent years, research has focused on specific adhesion molecules that participate in the activation and function of lymphocytes, especially the migration of these cells to sites of inflammation. In particular, the integrin, very late activation antigen (VLA)-4, has been implicated in mediating adhesion and migration of immune cells through interaction with its ligand, vascular cell adhesion molecule (VCAM)-1. VLA-4 is comprised of {alpha}4/ß1 and is critical in mediating Th-1 cell migration in the animal model of MS, experimental autoimmune encephalomyelitis, and has been the target of several recent clinical trials in MS. The humanized monoclonal antibody to {alpha}4 integrin, natalizumab (Tysabri, Biogen Idec/Elan), was recently approved in the United States for the treatment of relapsing MS. The authors discuss the mechanisms by which {alpha}4 integrins alter lymphocyte function as a rationale for anti-{alpha}4 integrin use in MS.

G.P.A.R. has received honoraria from Biogen Idec. H.-P.H. has received honoraria for speaking and consulting from Biogen Idec. A.C. has received honoraria in excess of $10,000 for speaking and consulting from Biogen Idec.

Received May 10, 2004. Accepted in final form January 10, 2005.




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