J Neuroimmunol 2002 Oct;131(1-2):147-59
Piraino PS, Yednock TA, Freedman SB, Messersmith EK, Pleiss MA, Vandevert C, Thorsett ED, Karlik SJ.
Department of Physiology, London Health Sciences Center, University of Western Ontario, N6A 5C1, London, ON, Canada
CNS leukocytic invasion in experimental allergic encephalomyelitis (EAE) depends on alpha4beta1 integrin/vascular cell adhesion molecule-1 (VCAM-1) interactions.
A small molecule inhibitor of alpha4beta1 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 alpha4beta1 integrin caused a sustained reversal of disease pathology in chronic EAE and may be similarly useful in MS.