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Effective Antigen-Specific Immunotherapy in the Marmoset Model of Multiple Sclerosis

Hugh I. McFarland^1,*, Adrian A. Lobito^*, Michele M. Johnson^*, Gregory R. Palardy^*, Christina S. K. Yee^*, E. Kay Jordan, Joseph A. Frank, Nancy Tresser, Claude P. Genain, John P. Mueller^2,¶, Louis A. Matis^¶ and Michael J. Lenardo^3,*

^* Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Laboratory of Diagnostic Radiology Research and Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892; Department of Neurology, University of California, San Francisco, CA 94143; and ^¶ Alexion Pharmaceuticals, Inc., New Haven, CT 06511

Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates.

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