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Abstract Details

A New Targeted Animal Model of Multiple Sclerosis in the Common Marmoset
MS and Related Diseases
P05 - (-)
180
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) in rodents is the most frequently used animal model of multiple sclerosis (MS). EAE induced by active immunization in the common marmoset in general shows a fulminant disease course. This animal model is of particular interest in the pre-clinical phase of new compound's testing for MS and for assessing correlation of clinical outcome with MRI activity due to the similarities of the marmoset immune system with human and the MS-like appearance of the inflammatory demyelinating lesions. However, the often fulminant disease course and the complication of the model, do not allow a systematic testing of new treatments in this model.
DESIGN/METHODS: We established a new targeted EAE in the common marmoset. White matter lesions in marmosets were sterotactically induced by injection of pro-inflammatory cytokines in animals that were immunized subclinically with myelin oligodendrocyte glycoprotein (MOG). Lesion development was followed by magnetic resonance imaging (MRI). The lesions were analyzed at different time points after cytokine injection allowing pathology and MRI correlation.
RESULTS: At the injection site of cytokines, confluent inflammatory demyelinating lesions developed that strongly resembled human MS lesions. There was extensive T cell and macrophage infiltration with demyelination and acute axonal damage. Demyelination was seen in the white and grey matter. Signs of early remyelination were also present.
CONCLUSIONS: In conclusion, our data present a new targeted EAE model in the common marmoset that will allow evaluating the therapeutic effects of compounds for the treatment of MS and provide better prediction tool of the clinical effects. Lesions can be treated at different stages of their development. This will broaden the pre-clinical evaluation of new treatments in MS.
Authors/Disclosures
Wolfgang Brueck, PhD (Zentrum Pathologie)
PRESENTER
Dr. Brueck has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Peter A. Calabresi, MD, FAAN (Johns Hopkins University) Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.