Tysabri® (natalizumab)

Natalizumab (Tysabri) is a humanized monoclonal antibody that binds to alpha-4 integrin expressed on the surface of activated T-cells. Alpha-4 integrin is a selective adhesion molecule that facilitates adhesion and subsequent leukocyte migration into areas of inflammation. Pre-clinical data has demonstrated the benefits of integrin inhibition, including mucosal healing and a reduction of inflammation. Leukocyte adhesion in endothelial cells is a multistep process that involves chemokine receptors and active integrins. Ultimately, natalizumab blocks both alpha-4 subunit of alpha-4 beta-1 (vascular cellular adhesion molecule of VCAM-1) and alpha-4 beta-7 (mucosal addressin [MAD] CAM-1). The site of action is not organ specific and other sites such as the brain, bone marrow, and kidneys are affected. This has led to studies of natalizumab in diverse chronic inflammatory diseases including MS and CD.