Prolonged reversal of chronic experimental allergic encephalomyelitis using a small molecule inhibitor of α4 integrin

Abstract

CNS leukocytic invasion in experimental allergic encephalomyelitis (EAE) depends on α4β1 integrin/vascular cell adhesion molecule-1 (VCAM-1) interactions. A small molecule inhibitor of α4β1 integrin (CT301) was administered to guinea pigs in the chronic phase (>d40) of EAE for 10, 20, 30 or 40 days. CT301 elicited a rapid, significant improvement in the clinical and pathological scores that was maintained throughout the treatment period. A progressive loss of cells in the spinal cord of treated animals confirmed the resolution of inflammation associated with clinical recovery. Therefore, prolonged inhibition of α4β1 integrin caused a sustained reversal of disease pathology in chronic EAE and may be similarly useful in MS.