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EMBARGOED UNTIL 9:45 A.M. PDT, TUESDAY, MAY 23, 2000
GENE THERAPY MAY HELP TREAT GASTROINTESTINAL ULCERS, UC IRVINE RESEARCHERS FIND
Findings in Rats Eventually Could Result in New Treatments for Ulcers
Irvine, Calif. -- Ulcers in the stomach and small intestine can be healed by injections of the genes that produce chemicals instrumental for repairing damaged tissue, according to a team led by researchers at UC Irvine's College of Medicine.
The findings, which resulted from studies conducted on rats, are believed to be among the first to show that gene therapy can heal damaged linings in the stomach and gastrointestinal tract. If effective on humans, the research could eventually be used to create better treatments for ulcers. The researchers presented their findings May 23 at "Digestive Diseases Week," the annual meeting of the American Gastroenterology Association in San Diego.
Dr. Sandor Szabo, professor of pathology and pharmacology at UCI and chief of the molecular medicine health care group at Long Beach Veterans Affairs Medical Center, and his colleagues found that a single injection of the genes that produce the chemicals, called growth factors, resulted in higher levels of growth factors and subsequent healing of ulcers within two weeks.
"To show that just a single dose of gene therapy can work, even in animals, is an exciting development in molecular medicine," Szabo said. "If this works in humans, it opens the door for a whole new class of treatments that heal stomach and intestinal ulcers more effectively than current therapies."
Szabo and his team found that rats given intravenous or intestinal injections of the genes that control two key growth factors, VEGF and PDGF, produced higher levels of those tissue-repairing chemicals; the ulcers were healed within two weeks of the injection of genes. VEGF, short for vascular endothelial growth factor, and PDGF, short for platelet-derived growth factor, help injured tissues heal by building new blood vessels and reconnecting cells damaged by trauma or disease.
The single injection indicates that gene therapy, if equally effective in humans, would involve fewer dosages of medicine than current therapies. Currently, antibiotic therapy usually requires about three doses a day and VEGF and other growth factors require one injection every day for several weeks to treat ulcers. In addition, antacids and other acid-inhibiting drugs usually must be taken over a lifetime.
"This study shows that VEGF, PDGF and the genes that produce them play an important role in ulcer healing," Szabo said. "If we can use gene therapy to increase the levels of these growth factors so that just enough is produced to induce healing, we could eventually design a gene-based drug that treats ulcers."
Gastrointestinal ulcers were traditionally considered to be caused by psychological stress; they are now associated with a bacteria called H. pylori. Recently, researchers have begun looking at the role played by proteins in the gastrointestinal system in the healing process. Since genes control the production of proteins in the body, it is possible to use these genes to treat disease by altering the activity of certain proteins.
The researchers are now trying to determine which genes play roles in ulcer development and healing, and are continuing to work to see how these genes also may be used to treat gastrointestinal disorders.
"We need to see what other genes control the healing process and determine how proteins and other chemicals in the gastrointestinal tract are produced and controlled," Szabo said. "This knowledge will help us decide which growth factors or genes are the most important in repairing ulcers and treating other diseases."
Gene therapy - using genes to treat inherited diseases and other disorders in which genes play a role but for which there is no known cure - is considered by many scientists to be the next frontier in medicine. It also may be valuable in reversing the course of disease without invasive surgery or drugs with severe side effects.
Szabo's colleagues include Xioming M. Deng, Martin R. Jadus, Tetyana Khomenko, Masashi Yoshida, Meahardt Herlyn, Mark Nesbit, Niroko Matsumoto and Warner H. Florsheim at UCI, the VA Medical Center, and the Wistar Institute in Philadelphia.
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Contact: Andrew Porterfield
(949) 824-3969
[email protected]
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