Leading pharmaceutical companies are attempting to developtreatments for inflammatory diseases by offsetting the harmfuleffects of leukotrienes.

Leukotrienes -- low-profile, high-potency locally reactinghormones in the immune system -- are the allegedperpetrators of asthma, psoriasis, rheumatoid arthritis,ulcerative colitis and other incurable inflammatory diseases.

Seven leading pharmaceutical companies, including G.D. Searle& Co., Ciba-Geigy Ltd. and SmithKline-Beecham plc, reportedtheir latest therapy-oriented research on leukotrienes to therecent 204th National Meeting of the American ChemicalSociety.

The clinically significant leukotriene variant, LTB4, is "one ofthe most potent attractants for neutrophils known," saidmedicinal chemist Stevan W. Djuric of Searle R&D in Skokie, Ill."It releases enzymes that promote inflammation and tissuedestruction."

LTB4 mobilizes vast armies of neutrophils, the body's mostnumerous white blood cells, to mount an inflammatorycounterattack at the site of an injury or antigenic invasion.

"Leukotrienes, especially LTB4," Djuric told BioWorld, "are aproper target for the pharmaceutical industry." The industry'sstrategy is two-pronged: to synthesize a LTB4 receptorantagonist to prevent the leukotriene from docking onneutrophils, and to synthesize enzyme inhibitors to blockrelease of 5-lipoxygenase, which is the first specific enzyme inthe biosynthesis of LTB4.

Searle is pursuing the first strategy, and has had a first-generation receptor antagonist against the LTB4 receptor onneutrophils in Phase II clinical trials since early this year.

At ICI Pharmaceuticals Group, Robert T. Jacobs' team hasprepared ICI 204,219, an antagonist to the LTB4 receptor, fortreating asthma. The compound was in Phase II trials in Europeand the U.S. six months ago, and has "made progress since,"says ICI spokesman Joel Taul.

Enter Ciba-Geigy of Basel, Switzerland. That company's M.Gerspacher told the ACS meeting in Wash. D.C., that "based onthe structure of ICI 204,219, a new potent and selectivepeptide-leukotriene antagonist has been synthesized."

At SmithKline-Beecham, Jerry L. Adams and colleagues have a5-lipoxygenase inhibitor poised as "a candidate for clinicaldevelopment."

Also participating in the leukotriene sweepstakes are Rhone-Poulenc Rorer, Hoechst-Roussel Pharmaceuticals and Schering-Plough Research Institute.

-- David N. Leff Science Editor

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

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