Natalizumab for Multiple Sclerosis: A Case in Point for the Impact of Translational Neuroimmunology.
Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α4-integrin. Representing the enormous success of a molecular targeted approach, natalizumab was the first mAb approved for the treatment of relapsing-remitting multiple sclerosis. However, only a few months after its approval, natalizumab was withdrawn from the market because of an unanticipated life threatening adverse effect: progressive multifocal leukoencephalopathy. Natalizumab was later reintroduced with required adherence to a strict monitoring program. In this article, we review the bench-to-bedside journey of natalizumab, along with the lessons learned from postmarketing studies.
Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.|Neurology Section, VA North Texas Health Care System, Medical Service, Dallas VA Medical Center, Dallas, TX 75216.
Afsaneh
0000-0002-8866-6426
A
Shirani
Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390; and olaf.stuve@utsouthwestern.edu.|Neurology Section, VA North Texas Health Care System, Medical Service, Dallas VA Medical Center, Dallas, TX 75216 olaf.stuve@utsouthwestern.edu.
Olaf
O
Stüve
D002986:Clinical Trials as Topic; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D039441:Integrin alpha4 / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects; D007968:Leukoencephalopathy, Progressive Multifocal; D009103:Multiple Sclerosis / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology; D000069442:Natalizumab / Q000009:adverse effects / Q000627:therapeutic use*; D015213:Neuroimmunomodulation / Q000187:drug effects; D012307:Risk Factors; D057170:Translational Research, Biomedical
D007155:Immunologic Factors; D000069442:Natalizumab; D039441:Integrin alpha4