Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Evaluation of the Effects of a New Drug on Brain Leukocyte Infiltration in an Experimental Model of Autoimmune Encephalomyelitis

Author(s): A. Mangas, R. Covenas, D. Bodet, M. P. Dabadie, G. Glaize, M. Geffard.

Abstract:

Experimental Autoimmune Encephalomyelitis (EAE) was induced for the evaluation of a new drug candidate (GEM-SP) for multiple sclerosis. Using immunocytochemical techniques with a pan-leukocyte marker, "anti-CD 45", differential leukocyte infiltration was compared in different experimental groups: 1) EAE-immunized rats treated with GEM-SP; 2) EAE-immunized rats treated with NaCl; 3) EAE-immunized rats treated with free constituents (not linked to inert carrier protein) and the inert carrier protein of GEM-SP. The results were conclusive: a very high degree of infiltration was observed in groups 2 and 3. Compared with these, group 1 showed a very poor leukocyte infiltration. Thus, the effect of GEM-SP against leukocyte infiltration was very strong, suggesting a decrease of the blood brain barrier permeability. Moreover, the same composition of GEM-SP (non-linked) was poorly active against leukocyte infiltration. The effect of GEM-SP therefore on the blood brain barrier appears to be very effective, rendering it less permeable to leukocyte infiltration and decreasing leukocyte infiltration per se and/or it is also possible that GEM-SP could play an immunomodulator role. The present results suggest GEM-SP as a new potential drug candidate for the treatment of multiple sclerosis.

Keywords: GEM-SP drug, leukocyte infiltration, experimental autoimmune encephalomyelitis (EAE), blood brain barrier, (BBB), multiple sclerosis (MS), immunohistochemistry, autoimmunity, immunomodulator, pan-leukocyte marker (anti-CD 45)

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2006
Page: [138 - 148]
Pages: 11
DOI: 10.2174/157018006776286943
Price: $58