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HOUSTON—(Feb. 4, 2002)—It started with a basic physiology question in the 1980s: How does the stomach avoid being consumed by its own powerful digestive acids?
Twenty years of research pointed a University of Texas Medical School at Houston scientist toward a solution to a nettlesome problem - protecting the digestive tract from the corrosive side effects of popular pain-relieving, anti-inflammatory drugs such as ibuprofen and aspirin.
Take a natural substance found in soy lecithin that is very similar to protective substances in the stomach lining, blend it with ibuprofen or aspirin, and you get a pain-relieving medication that's easy on the stomach, less expensive than popular alternatives, and appears to work better than the original drug does by itself, said Lenard M. Lichtenberger, Ph.D., professor of integrative biology and pharmacology, and founder of the recently formed GrassRoots Pharmaceuticals LLC.
Lichtenberger and colleagues at GrassRoots are developing new versions of ibuprofen and aspirin, members of a class of medication known as non-steroidal anti-inflammatory drugs (NSAID).
"We have a cost-effective and natural approach," Lichtenberger said. "Our hope is that the timing is right in the NSAID market to offer a new outlook." That market is estimated at $8 billion annually, with most sales for arthritis pain relief and cardiovascular risk reduction (daily use of aspirin).
The key to GrassRoots' efforts, Lichtenberger said, is phosphatidylcholine (PC), which happens to be concentrated in enriched soy lecithin. PC is the principal surface-active lipid, long known to play a significant role in cell membrane structure and lung function. Lichtenberger and colleagues established in the early 1980s that PC is normally present in the stomach's mucus lining, providing water-repellent properties that protect against digestive acids. They also demonstrated in a paper in Science that these protective barrier properties can be fortified by taking purified or synthetic PC by mouth.
Twenty to 40 percent of regular users of NSAIDs suffer gastrointestinal side effects ranging from nausea, diarrhea and heartburn to ulcers and gastrointestinal bleeding. Lichtenberger and colleagues found that these medications bind to and weaken the natural PC stomach lining, reducing its water-repellent effect. This damage opens the door to the gastrointestinal side effects.
"So, what would happen if we combined NSAIDs with PC?" Lichtenberger said. "We believed such a combination would not attack the stomach lining." Subsequent research, first using animals and more recently in a small clinical trial with human subjects, verified that hypothesis. PC-enriched NSAIDs reduced gastrointestinal side effects by 85 percent in rats and by an average of 68 percent in people.
Early findings point to a bonus: the combination might strengthen the drugs' anti-inflammatory, clot-busting, fever- and pain-relieving effects. "We hoped it would merely preserve therapeutic activity while reducing side effects. To our delight, we demonstrated that NSAIDs were more active when they are combined with PC," Lichtenberger said.
A clinical trial has been completed for an aspirin-PC combination, with promising results that were published in the American Journal of Gastroenterology. The National Institutes of Health has funded a clinical trial for a PC-ibuprofen combination, which is expected to start this summer.
GrassRoots' next step is to organize and finance the larger, long-term clinical trials that will be needed to make meaningful claims for the combinations in accordance with FDA regulations. GrassRoots expects this financing will come from the investment community. The company has an option agreement with UT-Houston for an exclusive worldwide license for 14 patents, half developed by Lichtenberger and half sub-licensed from other companies, and the rights to associated technology.
"Our hope is to put a drug on the market in four years," Lichtenberger said. The plan is to develop the drugs to the point they can be licensed to a pharmaceutical company capable of taking them to market. Four years would be a fairly swift progression, but Lichtenberger believes the PC blends of aspirin and ibuprofen have a significant advantage: they merely add a natural substance (lecithin) to two well-established drugs. Lecithin has a Generally Regarded As Safe designation by the U.S. Food and Drug Administration.
The NSAID market is highly competitive, with a new class of drugs, the cyclooxygenase (COX) inhibitors, in vogue. These medications inhibit the prostaglandin COX-2, which is produced at the site of a patient's inflammation, while leaving intact COX-1 found in the GI system and thought to have a protective role. The new medications are expensive, and face their own questions regarding GI, cardiovascular and renal side effects, Lichtenberger noted.
The GrassRoots option agreement is designed to convey one third ownership in the company to UT-Houston when a permanent licensing deal is reached, said UT-Houston Office of Technology Management Director Bruce Butler, Ph.D. "This promising spin-off company is one of several the university has been working on as we move to convert our scientific discoveries into improved therapies for patients," said Butler, who also is vice chairman of anesthesiology in the UT-Houston Medical School. OTM last year achieved substantial gains in inventions disclosed by faculty, option/licensing agreements, and royalty and other income generated.
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