This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Piraino, P S Articles by Karlik, S J Search for Related Content PubMed PubMed Citation Articles by Piraino, P S Articles by Karlik, S J Social Bookmarking                   What's this?

Suppression of acute experimental allergic encephalomyelitis with a small molecule inhibitor of 4 integrin

Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, Room 223, London, ON, Canada N6A 5C1

T A Yednock

Elan Pharmaceuticals, Inc., 800 Gateway Boulevard, South San Francisco, CA, 94080, USA

S B Freedman

Elan Pharmaceuticals, Inc., 800 Gateway Boulevard, South San Francisco, CA, 94080, USA

E K Messersmith

Elan Pharmaceuticals, Inc., 800 Gateway Boulevard, South San Francisco, CA, 94080, USA

M A Pleiss

Elan Pharmaceuticals, Inc., 800 Gateway Boulevard, South San Francisco, CA, 94080, USA

S J Karlik

Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, Room 223, London, ON, Canada N6A 5C1, skarlik{at}uwo.ca

Purpose: To determine the efficacy of a small molecule inhibitor of ₄ 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-₄ integrin 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-₄ 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).

Key Words: 4 integrin • experimental allergic encephalomyelitis • magnetic resonance imaging • multiple sclerosis • small molecule • therapeutic

Multiple Sclerosis, Vol. 11, No. 6, 683-690 (2005)
DOI: 10.1191/1352458505ms1223oa


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?