November 13, 1998

Symposium to probe therapeutic options of “super aspirins”

Symposium to probe therapeutic options of "super aspirins"

New "super aspirins" that promise relief from pain and inflammation without stomach upset have captured recent news headlines and will continue to do so as the first wave of these new drugs hits the market next year.

Development of these drugs ‹ expected to generate sales of $12 billion in their first year ‹ are a direct result of years of research into the biochemical pathway arising from arachidonic acid. This field of biology also has important implications for preventing cancer, Alzheimer's and heart disease.

Vanderbilt University Medical Center scientists have long been leaders in arachidonic acid biology, and VUMC will be the site of a one-day scientific symposium on Nov. 17 exploring the new therapeutic opportunities emerging from recent discoveries in this field.

The symposium will feature a keynote lecture honoring Dr. Allan D. Bass, professor of Pharmacology, emeritus, and delivered by Philip Needleman, Ph.D., a pioneer in the development of these new drugs, called COX2 inhibitors. Previously on the faculty at Washington University-St. Louis, Needleman is senior vice president and chief scientist for Monsanto Co., and president for research and development at G.D. Searle and Co.

"Dr. Bass can arguably be credited as the catalyst for a rich body of work in arachidonic acid biology at VUMC, beginning with his development of Clinical Pharmacology to link the bench to the beside and with his recruitment to the faculty of Dr. John A. Oates, who chose arachidonic acid metabolism and biology as his research area," said Lee E. Limbird, Ph.D., associate vice-chancellor for Research.

"We are pleased to host this symposium to explore what are among the most exciting therapeutic advances coming out of the laboratory today and to honor Dr. Bass for his role in placing VUMC at the vanguard of this field of science."

Much of the latest advances in arachidonic acid research have focused on the enzymes cyclooxygenase 1 and 2 (COX1 and COX2), which modify arachidonic acid to produce prostaglandins. COX1 is constantly present in all tissues, and its prostaglandin products are responsible for such duties as protecting the stomach lining and keeping the kidneys functioning properly. On the other hand, COX2 is produced by the body only under certain circumstances, and its prostaglandin products lead to inflammation, pain and fever.

The COX2 inhibitors now in development temporarily block only COX2 with no effect on COX1.

The Nov. 17 symposium will be capped off by an evening roundtable discussion about the new COX2 inhibitors and their implications for arthritis treatment and prevention of cancer and Alzheimer's, as well as other therapeutic opportunities emerging from arachidonic acid research.

Moderated by veteran television journalist Jim Hartz, the discussion will be entitled "Building a Better Aspirin: The Journey from Discovery to Drugstore."

In addition to Needleman, its participants will include:

Lawrence J. Marnett, Ph.D., Mary Geddes Stahlman Professor of Cancer Research and director of research for the Vanderbilt Cancer Center. Marnett's laboratory reported last spring that it had developed a new COX2-selective inhibitor that is the first to irreversibly disable the enzyme.

Dr. Raymond N. DuBois Jr., Mina Cobb Wallace Professor of Gastroenterology and Cancer Prevention and director of Gastroenterology, whose laboratory is focused on the role of COX2 in the development of colon cancer and the potential to prevent the disease with COX2 inhibitors.

Dr. L. Jackson Roberts II, professor of Pharmacology and Medicine, who with his colleague Dr. Jason D. Morrow, has discovered a method to gauge the effects of oxidation in the body by measuring a type of prostaglandin called isoprostanes, produced not by enzymes but by oxygen-free radicals.

T. Forcht Dagi, M.D., M.P.H., M.B.A., president of Cordova Technology Ventures, a venture capital company helping discoverers identify financial resources to test the suitability of their findings for therapeutic application.

Mayor Phil Bredesen, a scientist by training and a successful leader and businessman in the health care industry.

The roundtable discussion will be 5 p.m.-6:30 p.m. in 208 Light Hall. The keynote address and other presentations earlier in the day will be in 214 Light Hall.

The afternoon schedule is as follows:

o 1 p.m. ‹ welcome by Limbird.

1:05 p.m. ‹ Cancer and Eicosanoids: Insights from Examining Immediate Early Gene Expression Unique to Colon Carcinoma: DuBois.

o 1:25 p.m., Novel Arachidonic Acid Metabolites in Cellular Proliferation: Dr. Jason D. Morrow, associate professor of Medicine and Pharmacology.

o 1:45 p.m. ‹ Building a Better Aspirin: Marnett.

o 2:05 p.m. ‹ Novel Roles for PGE2 Receptors Revealed by Targeted Gene Strategies: Richard M. Breyer, Ph.D., associate professor of Medicine and assistant professor of Pharmacology.

o 2:25 p.m. ‹ Novel Stereo-Specific Lipoxygenase Pathways: Alan R. Brash, Ph.D., professor of Pharmacology.

o 2:45 p.m. ‹ Novel Arachidonic Acid Pathways in Renal Epithelia: Jorge H. Capdevila, Ph.D., professor of Medicine and Pharmacology.

o 3:05 p.m. ‹ Isoprostanes, Non-Enzymatic Metabolites of Arachidonic Acid, Offer and In Vivo Monitor for Oxidative Stress: Roberts.

o 3:25 p.m. ‹ Reception to honor Bass and Needleman as the Allan D. Bass Lecturer

o 3:45 p.m. ‹ Keynote Lecture: Therapeutic Frontiers in Eicosanoid Biology; Needleman.