Natalizumab: Perspectives from the Bench to Bedside

Probably no other disease-modifying drug for multiple sclerosis has a more fascinating story than natalizumab from both the bench to bedside perspective and the postmarketing experience standpoint. Natalizumab is a monoclonal antibody that inhibits the trafficking of lymphocytes from the blood into the central nervous system by blocking the adhesion molecule alpha 4-integrin. Natalizumab was approved as a disease-modifying drug for relapsing remitting multiple sclerosis only 12 years after the discovery of its target molecule a time line that is rather fast for drug development. However, a few months after its U.S. Food and Drug Administration approval, natalizumab was withdrawn from the market because of an unanticipated complication-progressive multifocal leukoencephalopathy. It was later reinstated with required adherence to a strict monitoring program and incorporation of mitigation strategies.