DURHAM, N.C. -- Sphinx Pharmaceuticals Corp. and theWashington University School of Medicine in St. Louisannounced Wednesday a five-year collaboration to developnovel treatments for cardiovascular and inflammatory diseases.

The Sphinx-WU collaboration is based on research into a groupof human enzymes known as phospholipases A2 (PLA2).

PLA2 enzymes convert specific lipid molecules present in thecell membrane into a lipid product known as arachidonic acid.The production of arachidonic acid from myocardial cellsmaking up the heart muscle contributes to the buildup of fattyacids that can cause heart attacks and other heart problems.

The PLA2 enzyme that was found in the platelets is alsobelieved to be in white blood cells and is responsible forinflammation.

The goal of the collaboration is to inhibit or control the releaseof arachidonic acid by following the path not taken by mostprevious researchers.

While PLA2 enzymes produced outside the cell have long beena target for research within the pharmaceutical industry, theSphinx-WU collaboration will focus on intracellular forms ofPLA2.

"The traditional approach of looking for inhibitors ofextracellular PLA2 enzymes has not yielded any usefultherapeutic agents," Richard Gross, professor of medicine,chemistry, molecular biology and pharmacology at WashingtonUniversity and leader of the collaboration, told BioWorld.

Gross said proteins resembling what are now known asextracellular PLA2 enzymes were originally thought to liberatearachidonic acid when mammalian cells were activated. He saidit is becoming increasingly evident that is not the case.

"What everyone is after is to turn off arachidonic acid releasein activated cells," Gross said. He thinks the better approach toturning off arachidonic acid release is to target intracellularPLA2 enzymes.

Gross headed research that discovered two of the three knownintracellular PLA2 enzymes: a calcium-independentintracellular PLA2 enzyme in myocardial cells and a calcium-responsive PLA2 in platelets.

Gross said it is difficult to predict when the collaboration coulddeliver its first products to market, but that it could take aslittle as five years.

Diseases targeted by the collaboration include cardiac ischemia,arrhythmias, myocardial infarction, stroke, pulmonaryembolism, deep venous thrombosis, arthritis and asthma,according to Sphinx.

Under the terms of the agreement, Sphinx will fund a minimumof $5 million for research at the university. The companyreceives licensing rights to university patent applications andlicensing or option rights to the university's interest in futurepatents arising from the research program.

Carson Loomis, Sphinx's vice president of research, said twopending patents are initially included in the collaboration.Sphinx will also obtain exclusive development and marketingrights to all therapeutic candidates that result from theagreement with the university to receive royalties on productsales.

Sphinx was at first reluctant to get involved in PLA2 research,Loomis said. "We did not want to involve ourselves in a fieldwhere companies were not turning out products -- not unlesssomebody gave us a giant step forward on everybody else.Richard Gross did that."

Sphinx plans to add 12 people specifically for the project andhas hired Robert Crowl, who worked on extracellular PLA2 atHoffmann-La Roche, to head it part of the collaboration.

-- Steve Payne BioWorld Staff

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

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