Discoveries by UAB and Florida scientists may help transplanted organs survive longer

04/29/05

BIRMINGHAM, Ala. Scientists may have found a way to dramatically slow organ transplant rejection by as much as several years.

That's the promising implication of an animal study carried out by researchers at the University of Alabama at Birmingham (UAB) and the University of Florida (UF) published in today's (May 2) issue of Proceedings of the National Academy of Sciences.

The research team reported that they have identified the biological pathway of a potent molecule that could delay rejection of transplanted organs by preventing blood-vessel deterioration.

"One of the principal problems for kidney transplantation is organ availability," said Mark A. Atkinson, Ph.D., a study co-author and director of the Center for Immunology and Transplantation Research at UF. "That occurs in part because after several years, people with kidney transplants often lose function of the organ. With about 60,000 people on the waiting list for a transplant, it would help immensely to find a way to reduce a patient's need for a second or third kidney."

The helpful molecule, IL-10, has anti-inflammatory, immunosuppressive and other properties that help keep blood vessels healthy. Chronic vascular rejection, characterized by thickening of the interior lining that eventually chokes off the blood supply, is a major cause of the loss of function in solid organ transplants.

The study, carried out in rat models, also showed that a single muscular injection of the molecule, interleukin-10 (IL-10), carried in a gene delivery vector, or mechanism, could provide long-term therapeutic effects.

Anupam Agarwal, M.D., director of the UAB Nephrology Research and Training Center and senior author of the report, said the group found that IL-10 was active through the heme oxygenase-dependent (HO-1) biological pathway between cells.

"We found that one dose of IL-10 delivered using a viral vector delays the vascular disease from occurring," Agarwal said. "If the HO-1 pathway is blocked, the protective effects of IL-10 are lost. The delay in vascular disease shown in this study could after more research and possible clinical trials in human beings offer the benefit of at least several additional years of health for transplanted organs."

A key to the single-injection strategy, Atkinson said, "was the use of adeno-associated virus as a way to deliver IL-10 into the body, allowing sustained levels of the molecule to be persistently secreted into the blood stream.

The next step will be to evaluate the treatment to try to protect kidney transplants in non-human primates and if successful there, go on to clinical trials in humans, said Agarwal.

Source: Eurekalert & others

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