Prolonged reversal of chronic experimental allergic encephalomyelitis using a small molecule inhibitor of alpha4 integrin.
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.
Piraino
P S
PS
Department of Physiology, London Health Sciences Center, University of Western Ontario, London, ON, Canada.
Yednock
T A
TA
Freedman
S B
SB
Messersmith
E K
EK
Pleiss
M A
MA
Vandevert
C
C
Thorsett
E D
ED
Karlik
S J
SJ
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006168:Guinea Pigs; D039441:Integrin alpha4; D007700:Kinetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013116:Spinal Cord / Q000473:pathology
D016207:Cytokines; D012333:RNA, Messenger; D039441:Integrin alpha4