MaRGA Meeting, 2004: Abstracts

17: Physiology and Immunology

Primate Models of Inflammation with Emphasis on Multiple Sclerosis

C. Genain

Affiliation: Department of Neurology, University of California, San Francisco, CA

Models that adequately reflect the complexity of human multiple sclerosis (MS) are needed, especially for pre-clinical testing of immunomodulatory drugs. A unique experimental system to study MS has been created in the New World common marmoset Callithrix jacchus jacchus (C. jacchus). Following immunization with myelin, these monkeys develop a chronic, relapsingremitting form of experimental allergic encephalomyelitis (EAE), which pathologically, recapitulates the hallmark features of lesions of human MS. The MS-like lesion in C. jacchus results from a complex immune response against myelin antigens, and requires both T cells and pathogenic antibodies. Studies of C. jacchus EAE have permitted the identification of a major target for pathogenic autoantibodies in MS, the myelin/oligodendrocyte glycoprotein. Other advantages of the model include a natural bone marrow chimerism, which permits T cell adoptive transfers between siblings, and the possibility of using different antigens to produce either inflammatory or demyelinating phenotypes of EAE. Despite their small size, sequential in vivo imaging and immunological studies are possible in these monkeys, and have been used to monitor efficacy in preclinical trials. In addition and similar to tamarins, C. jacchus marmosets have a large deletion in the major histocompatibility class I gene region which perhaps favors susceptibility to spontaneous autoimmune diseases such as thyroiditis and inflammatory bowel disease. Due to close phylogeny and high homology of immune and nervous system genes with humans, this model has fast-tracked the development of novel therapeutics for MS such as B cell targeted therapy.

MaRGA gratefully acknowledges the generous contribution of Harlan, Inc. in sponsoring this invited speaker.