Experimental autoimmune encephalomyelitis in the common marmoset: a novel animal model for multiple sclerosis

Multiple sclerosis (MS) is a major cause of disability in young adults affecting approximately 15,000 people in The Netberlands. Critical aspects of the disease have been modeled by experimental autoimmune encephalomyelitis (EAE) in animals. The vast majority of investigators use rats and mice for the unraveling of tbe MS immunopathogenesis and for tbe development of new tberapies. However, despite decades of intensive research, the primary cause of MS is still unknown and no curative treatment exists. With the development of EAE in the common marmoset, a new nonhuman primate model for MS has become available tbat seemed superior to tbe existing rodent and nonhuman primate models in many aspects (Massacesi. 1995). The first experiments performed at the BPRC confirmed this view ('r Hart. 1998). The etbical constraints for using nonhuman primates demand that such a model is used only for purposes that can not be investigated otherwise. The prime rationale for nonhuman primate models of human disease is tbe possibility to evaluate potentially effective therapies tbat do not sufficiently work in rodents. At the time tbat our studies were started, only the EAE model in rhesus monkeys could be regarded as being of sufficient scientific maturity. However, both clinically and neuropathologically this model did not sufficiently resemble chronic MS. It was therefore decided to further develop the marmoset EAE model and to scientifically explore whether tbis model can substantially contribute to our knowledge on the ethiopathogenesis ofMS and to the development of new therapeutics for this disease. The aims of the studies described in this thesis were: I. To investigate the immunopatbogenic mechanisms leading to the specific inflammatory demyelination of the central nervous system (CNS). 2. To investigate the genetic basis of the I 00% disease incidence observed in our outbred colony. 3. To validate the model for therapeutic purposes using antibody-mediated intervention in patbogenic pathways.

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