A novel angiogenesis inhibitor suppresses rat adjuvant arthritis.
Rat adjuvant arthritis (AA) is an animal model of rheumatoid arthritis in which pannus formation and destruction of joints occur after immunization with complete Freund's adjuvant. Neovascularization is present within the synovium and may be critical for pannus growth. In this study the effects of a novel angiogenesis inhibitor, AGM-1470, on AA were evaluated. Lewis rats were immunized with CFA to induce arthritis. AGM-1470 treatment was initiated prior to arthritis onset (preventative protocol) or administered to rats with established disease (suppressive protocol). The severity of synovitis and the immunologic status of all rats were then evaluated. Using clinical and radiographic criteria, AGM-1470 significantly reduced arthritis incidence (preventative protocol) (P < 0.01) and disease severity (both protocols, P < 0.001, compared to controls) without affecting T cell function in vitro or phenotype in vivo. Additionally, histologic sections from control rats revealed marked pannus formation, destruction of bone/cartilage, and neovascularization. These findings were absent in AGM-1470-treated rats. AGM-1470 may offer a new treatment option for rheumatoid arthritis and other angiogenesis-dependent diseases.
Peacock
D J
DJ
Department of Medicine, UCLA School of Medicine 90024-1670, USA.
Banquerigo
M L
ML
Brahn
E
E
D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D003510:Cyclohexanes; D005260:Female; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol