Clinical studies on two children who suffered recurrent seriousinfections because they couldn't mount a normal immuneresponse have demonstrated that they lack key cell adhesionmolecules.
Researchers from the Rambam Medical Center in Haifa, Israel,and Cytel Corp. (NASDAQ:CYTL) of San Diego reported theirresults Thursday in the New England Journal of Medicine.
This rare disorder, which the scientists termed leukocyteadhesion deficiency type 2 (LAD-2), is apparently caused by adeficiency of sialyl-Lewis X (SLex), a carbohydrate moietyusually present on the surface of neutrophils.
Neutrophils are normally recruited to the site of inflammationby various factors that induce them to roll on blood vesselwalls, then adhere tightly and flow into the surroundinginflamed tissue.
The cell adhesion molecules E- and P-selectin, which arelocated on the surface of endothelial cells lining the bloodvessel wall, induce the neutrophil rolling. And the ligands forE- and P-selectin are the SLex moieties. Thus, if these aredeficient or missing, the neutrophils can't adhere and can't getto the site of inflammation.
"Based on our understanding of the role that the selectin-SLexinteraction plays in neutrophil recruitment," said JamesPaulson, vice president of research at Cytel and a co-author ofthe study, "we are developing drug candidates designed toinhibit this interaction for the treatment of acute inflammatorydiseases and reperfusion injury."
Cytel's lead candidate, CY1787, is a murine monoclonalantibody designed to block neutrophil binding to E-selectin. It'salready in Phase I clinical trials in Belgium and the UnitedKingdom, according to Deborah Goode, Cytel's associate directorof finance. CY1787 is being evaluated in these trials for treatingsepsis and for allergic rhinitis. Goode told BioWorld that Cytel iscurrently developing a humanized form of CY1787, calledCY1788. "We anticipate taking CY1787 only through Phase I,"she said.
Cytel is also developing a compound to block the P-selectinreceptor (CY1747), and one that will bind both E- and P-selectin receptors (CY1503).
-- Jennifer Van Brunt Senior Editor
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