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Release: Immediate

UI developing gene therapy to help reduce problems with organ transplants

IOWA CITY, Iowa -- Someday doctors may be able to reduce the risk of organ rejection in transplant patients, thanks to a gene therapy that University of Iowa researchers are designing.

While the UI research has focused on liver transplantation, the new therapy also could help to decrease the damage that heart attacks cause and may even be useful for preventing problems before they occur.

"This type of gene therapy for acquired disease is part of an emerging field of therapeutics," said John F. Engelhardt, Ph.D., UI associate professor of anatomy and cell biology, and the project's principal investigator. "Its application is not limited to the liver."

A team of UI investigators currently is using models to test the gene therapy as the group moves towards the therapy's clinical application for liver transplantation. Different elements of the UI research appeared in the June issue of Nature Medicine and more recently in the October issue of Hepatology.

The UI-designed gene therapy would target ischemia-reperfusion injuries. When organs in the body have reduced blood flow such as during transplants and heart attacks, they lack adequate oxygen to support life. While this aspect, called ischemia, is not itself significantly damaging to cells, when blood flow is re-established (called reperfusion), the high levels of oxygen create damaging compounds.

"These compounds can signal cells to commit suicide," Engelhardt said. "We have designed a gene therapy that creates a garbage disposal of sorts for clearing these damaging compounds from the body before cell death can occur."

Using an engineered defective common cold virus, the researchers transfer a therapeutic gene, called mitochondrial superoxide dismutase (MnSOD), to all liver cells in order to reduce ischemia-reperfusion induced damage.

"The application of this work will hopefully lead to treatments that can increase the success of organ transplantation," Engelhardt said. "The investigators are using similar approaches to reduce the damage caused by heart attacks as well."

By using the gene therapy as soon as possible after the heart attack occurs, physicians can hopefully help the damaged cells to repair themselves, Engelhardt said. This therapy also could help those at high risk of heart attacks by reducing damage from ischemic heart disease.

This type of gene therapy research is part of the UI's newly funded Gene Therapy Core Center, which Engelhardt will direct. The National Institutes of Health and the Cystic Fibrosis Foundation recently awarded the UI an $8 million, five-year grant to develop the center, which is expected to be operational by November. The UI is one of two institutions nationwide that received funding this fiscal year to establish such a center.

10/30/98