title: Natalizumab: bench to bedside and beyond.
abstract: Natalizumab has been available as a multiple sclerosis treatment for more than 5 years in Europe and the United States. Natalizumab was granted approval by the US Food and Drug Administration in 2004, only 12 years after its molecular target was cloned. Shortly after initial approval, natalizumab use was suspended pending a safety review when several natalizumab recipients were diagnosed as having progressive multifocal leukoencephalopathy. After the safety review, natalizumab was reintroduced to the market in 2006. Since then, more than 92,000 patients have been treated with the drug. Risk stratification algorithms and progressive multifocal leukoencephalopathy management strategies have been developed, which facilitate more personalized decision making and safer natalizumab use. This review article summarizes the evolution of natalizumab from target molecule discovery through regulatory approval, voluntary suspension, reapproval, and clinical use. The natalizumab story highlights both the opportunities and risks inherent in a novel biological therapy for a progressive neurologic disease.
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. rudickr@ccf.org
authors.forename: Richard
authors.initials: R
authors.lastname: Rudick
authors.forename: Chris
authors.initials: C
authors.lastname: Polman
authors.forename: David
authors.initials: D
authors.lastname: Clifford
authors.forename: David
authors.initials: D
authors.lastname: Miller
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000453:epidemiology; D000069442:Natalizumab; D011358:Product Surveillance, Postmarketing / Q000379:methods / Q000639:trends; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence / Q000639:trends
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab