Multiple sclerosis (MS) is a devastating autoimmune disease that is characterized by inflammation in the brain and spinal cord that damages the myelin sheath, thereby causing demyelination of neurons [1
]. Demyelination impairs neuronal signal transmission, which in turn results in various physical and cognitive disabilities such as sensory disorder, motor dysfunction, optic neuritis, and coordination problems. The disease worsens in many patients during relapses, and effective treatments to block the relapses remain limited. In this way, multiple sclerosis imposes a substantial economic burden across developed countries worldwide [4
Infiltration of the brain by autoreactive immune cells that originate in the peripheral circulation plays a central role in the pathogenesis of inflammation in MS [3
]. During the last decade, significant progress has been made in understanding how pathogenic leukocytes migrate from the periphery to the central nervous system (CNS). The critical roles played by a specific cell adhesion molecule, alpha4 integrin, in leukocyte-endothelial cell interactions at the blood brain barrier have been studied extensively in animal models, as well as in patients in clinical trials [6
]. It is worth noting that natalizumab (Tysabri), a blocking antibody to alpha4 integrin, was approved by the FDA in 2004 for the treatment of relapsing multiple sclerosis patients. This paper describes the molecular and structural bases for using anti-integrin therapy for multiple sclerosis and then discusses both the promise and problems with this treatment strategy including the importance of clinical pharmacovigilance in the risk management of natalizumab treatment.