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WSU Scientist Discovers Compounds To Limit Lung Disease

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A Wichita State University distinguished professor has developed two new classes of organic compounds that show promise in limiting damage caused by lung disease and possibly other inflammatory diseases.

The number of lives claimed by chronic lung disease has increased sharply - in 1979 it accounted for about 50,000 deaths; by 1992, the number of deaths reached 86,974.

The compounds, which recently were patented, are unique because scientists can change the makeup of the compounds, thereby changing their disease-fighting abilities.

"These are very versatile classes, which make them unusual," said William Groutas, WSU Endowment Association Distinguished Professor of Chemistry. That versatility means they may be modified to fight different enzymes occurring in other inflammatory or infectious diseases.

The compounds essentially block enzymes which cause connective tissue damage. When an individual has an inflammatory reaction, there is a massive migration of neutrophils, a type of white cell, to the inflamed site. The function of the neutrophils, as part of the immune system, is to wage war on the bacteria by ingesting it. The neutrophils then kill the bacteria by releasing enzymes. Occasionally some neutrophils become casualties in this war and the enzymes leak out, creating tissue damage, explained Groutas.

"There are certain proteins in the body that keep these enzymes at bay, but this defense system is overcome, overwhelmed in this diseased state."

The two classes of compounds Groutas has developed "are effective in blocking the migration of white cells to the site of inflammation," thus reducing the likelihood of mortally wounded neutrophils leaking enzymes and reducing the inflammation.

Preliminary animal studies, with promising results, have already been conducted by George Weinbaum, a colleague of Groutas who is chief of the research division in the department of medicine at the Graduate Hospital in Philadelphia. Another lab in Pennsylvania will conduct follow-up testing, using rats. The studies will focus only on the compounds' effects on lung disease. WSU will supply the compounds used in the animal studies.

The studies are being financed by a small but aggressive biotechnology firm, Sparta Pharmaceuticals Inc. located in Horsham, Pa., which focuses on serine protease inhibitors, such as the compounds Groutas has developed. WSU has entered a licensing agreement with Sparta.

If the animal studies continue to show success, the company will apply to the FDA to pursue human clinical trials. The time frame for completing the current animal studies is one year.

Borrowing a practice used by pharmaceutical companies, Groutas and his research team of post-doctorate, graduate and undergraduate students will develop "compound libraries" - producing thousands of compounds and then screening for the most potent derivative. "It's like looking in a gold mine to find the gold."

His work has been funded by grants awarded from 1982 to 1995 through the National Institutes for Health, and since 1994 through grants from Sparta Pharmaceuticals Inc.

Groutas has been working on developing compounds to combat inflammatory diseases, particularly those affecting lungs, since arriving at WSU in 1980. The patent he recently received was his second in this endeavor. It has been a long process, largely because of what Groutas calls "a small operation." Through the years, he has used his research as teaching and service tools, as well, working with a cadre of six to eight post-doctorate, graduate and undergraduate students and, adding in the summer, high school or community college science teachers and high school students. Because of turnover, Groutas also spends time training these individuals, in addition to directing the research.

Two articles on these two new classes of compounds were published in 1993 and in 1994 in Biochemical and Biophysical Research Communications. Now that the patent has been granted, Groutas will submit several more papers dealing with the subject. He also will present his work at a conference on this type of inhibitors in Baltimore Nov. 6-7.

Contact: William Groutas, (316) 978-3120, or groutas@wsuhub.uc.twsu.edu. * * * * *

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