Researchers reported Monday at the 65th Annual AmericanHeart Association Meeting in New Orleans that an anti-P-selectin antibody can protect against reperfusion injury inanimal models. The antibody, CY1747, developed by Cytel Corp.of San Diego, apparently inhibits the migration of neutrophils totissue that has been ischemic (deprived of blood and oxygen)during reperfusion.

It was already known that such migration of neutrophils couldlead to substantial and often irreversible tissue damage. ButUniversity of Washington researchers Robert Winn and JohnHarlan, using a rabbit transplantation model, and Allan Lefer ofThomas Jefferson University, using a cat myocardial ischemiamodel, have found that the cell adhesion molecule P-selectinmay play a critical role in recruiting those neutrophils to sitesof damaged tissue following reperfusion. By blocking P-selectinwith the CY1747 antibody, the researchers all found that theywere able to inhibit neutrophil migration, and thus protect thetissue.

P-selectin is expressed on the endothelial cells lining bloodvessel walls as well as on platelets, where it was firstdiscovered. But "it was only identified as an adhesion moleculeless than three years ago," said James Paulson, Cytel's vicepresident of research. And it takes certain biochemical signals-- thrombin, histamine, free oxygen radicals -- to activate P-selectin as a neutrophil-recruiter. Since thrombin is present atthe site of reperfusion injury and since there is a burst ofoxygen radicals when tissue that has lacked oxygen for anextended period of time is reperfused, Paulson explained that itmade sense to propose that P-selectin plays an important rolein reperfusion injury.

"CY1747 is currently in preclinical development, and webelieve it may prove efficacious in minimizing reperfusioninjury associated with such serious disorders as myocardialinfarction, stroke and organ transplantation," said Jay Kranzler,president and chief executive officer of Cytel (NASDAQ:CYTL).

Paulson told BioWorld that the only other adhesion molecule inadvanced development for treating reperfusion is BoehringerIngelheim's anti-ICAM, which is in Phase II trials. "ICAM is anadhesion molecule involved in a later-stage event in therecruitment of neutrophils," Paulson said, and Boehringer hastargeted its product for preventing lymphocyte recruitmentthat can lead to kidney transplant rejection.

Other potentially competing products, said Paulson, includeCentocor Inc.'s peptide-based P-selectin inhibitors andSynergen Inc.'s interleukin-1 receptor antagonists.

"This is a hot area," Paulson told BioWorld. "Selectins astherapeutic targets are of interest to many pharmaceutical andbiotech companies. We expect there will be increasedcompetition for directly competitive approaches to P-selectinsin the future."

Cytel's stock closed up $1 a share on Monday to $13.38.

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.

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