A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis

• Published in: The New England journal of medicine Vol. 348; no. 1; pp. 15 - 23
• Main Authors: Miller, David H, Khan, Omar A, Sheremata, William A, Blumhardt, Lance D, Rice, George P.A, Libonati, Michele A, Willmer-Hulme, Allison J, Dalton, Catherine M, Miszkiel, Katherine A, O'Connor, Paul W
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 02.01.2003
• Subjects: Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Brain - pathology; Cell adhesion & migration; Double-Blind Method; Female; Gadolinium; Humans; Magnetic Resonance Imaging; Male; Medical research; Medical sciences; Middle Aged; Multiple sclerosis; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; Natalizumab; Neurology; Neuropharmacology; Neuroprotective agent; NMR; Nuclear magnetic resonance; Pharmacology. Drug treatments; Statistics, Nonparametric; Human; Nervous system diseases; Relapse; Multiple sclerosis; Prognosis; Natalizumab; Radiologic sign; Treatment efficiency; Clinical form; Inflammation; Nuclear magnetic resonance imaging; Inflammatory disease; Integrin; Central nervous system disease; Double blind study; Clinical trial; Antagonist; Brain (vertebrata)
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa020696

Natalizumab is an antagonist of α 4 integrin, a very late adhesion antigen that is expressed on the surface of activated lymphocytes and monocytes. In this double-blind, placebo-controlled trial, the patients who received natalizumab had fewer new enhancing lesions on gadolinium-enhanced magnetic resonance imaging and significantly fewer relapses. Treatment with agents that inhibit adhesion of activated immune cells may offer benefits. Multiple sclerosis is a leading cause of chronic neurologic disability. 1 Several new therapies have been introduced in the past decade, 2 – 5 but additional effective treatments are needed to slow disease progression and reduce disability. The pathological hallmark of multiple sclerosis is multiple foci of inflammation and demyelination within the white matter of the central nervous system. The formation of these lesions may involve lymphocytes and monocytes that gain access to the brain parenchyma from the circulation by first adhering to vascular endothelial cells in regions of inflammation. 6 The glycoprotein α 4 β 1 integrin, also known as very late antigen . . .