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

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)