Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale

Neurology. 2005 Apr 26;64(8):1336-42. doi: 10.1212/01.WNL.0000158329.30470.D0.

Abstract

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 alpha4/beta1 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 alpha4 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 alpha4 integrins alter lymphocyte function as a rationale for anti-alpha4 integrin use in MS.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Cell Adhesion / drug effects
  • Cell Adhesion / immunology
  • Chemotaxis, Leukocyte / drug effects*
  • Chemotaxis, Leukocyte / immunology
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Integrin alpha4 / drug effects*
  • Integrin alpha4 / immunology
  • Integrin alpha4beta1 / antagonists & inhibitors
  • Integrin alpha4beta1 / immunology
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • Natalizumab
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Vascular Cell Adhesion Molecule-1 / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Integrin alpha4beta1
  • Natalizumab
  • Vascular Cell Adhesion Molecule-1
  • Integrin alpha4