BENEFIT OF INHIBITING SSAO IN RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

AM O’Rourke, EY Wang, L Salter-Cid, L Huang, A Miller, E Podar, HF Gao, DS Jones, and MD Linnik

Abstract

We have developed several series of potent and selective small molecule inhibitors of SSAO (AOC3/VAP-1) that also block trafficking of leukocytes to sites of inflammation. Blocking of SSAO-mediated leukocyte adhesion has recently been shown efficacious in several models of inflammatory diseases. We have examined the potential of SSAO inhibitors in neurological diseases, having previously demonstrated the efficacy of SSAO inhibition in a rat model of stroke. Here we show the effect of the small molecule SSAO inhibitor LJP 1207 (IC(50) human SSAO 17 nM; ratio IC(50) SSAO:MAO >5000), on relapsing-remitting experimental autoimmune encephalomyelitis (EAE), a mouse model that shares many characteristics with human multiple sclerosis. Clinical efficacy was observed when dosing with LJP 1207 was initiated either at the peak of initial flare or during remission. These data demonstrate the potential clinical benefit of small molecule anti-SSAO therapy in this model.

Published in
Journal Neural Transmission
June 2007
Volume 114, No. 6 pp 845-849