Suppression of acute experimental allergic encephalomyelitis with a small molecule inhibitor of α4 integrin.

Autor: Piraino, P. S., Yednock, T. A., Freedman, S. B., Messersmith, E. K., Pleiss, M. A., Karlik, S. J.
Předmět:
Zdroj: Multiple Sclerosis (13524585); Dec2005, Vol. 11 Issue 6, p683-690, 8p, 1 Black and White Photograph, 2 Diagrams, 2 Graphs
Abstrakt: Purpose: To determine the efficacy of a small molecule inhibitor of α4 integrin (CT301) at reversing the clinical, pathological and MR-detectable deficits associated with the acute phase of experimental allergic encephalomyelitis (EAE). Materials and methods: EAE was induced in 36 female Hartley guinea pigs, and the treatment period was from day 11 to day 17 post-immunization. Animals received either saline (n = 12), anti-α4integrin antibody (AN100226m; n = 12) or CT301 (n = 12). T2-weighted fast spin echo and T1-weighted pre- and post-contrast scans were performed at the beginning (day 11) and end (day 18) of the treatment period, and scored for cerebral inflammation and gadolinium enhancement. T1-weighted images were further analyzed to quantify this enhancement as a measure of blood–brain barrier integrity. Dissected CNS was evaluated for inflammation and demyelination. Results: CT301 successfully reversed two clinical indicators of disease over the course of the treatment period. These animals showed decreased T2-weighted abnormalities, as well as a reduction in gadolinium leakage on T1-weighted images. Meningeal and perivascular inflammation was decreased by anti-α4 integrin treatments. Conclusion: CT301 effectively reverses the clinical, pathological and MR-detectable deficits of acute EAE, and may therefore be a promising therapeutic agent in multiple sclerosis (MS). [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index