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Stanford researcher dusts off old drug; uncovers new anti-rejection properties

STANFORD, Calif. - Thirty years ago, researchers scooped some dirt on Easter Island and discovered bacteria that led to a potential anti-fungal drug. Little did they know that the drug - which languished on shelves after proving ineffective in early trials - would become popular in 1999 as a way to prevent rejection of transplanted organs.

Now, new studies from Stanford University Medical Center have found that the drug can also protect blood vessels of transplanted hearts, preventing the leading cause of heart transplant failure.

Randall Morris, MD, research professor and director of transplantation immunology in the Department of Cardiothoracic Surgery, elevated the drug - called sirolimus - from the brink of obscurity to its current role in transplantation. Morris will present results from his recent studies April 30 at the American Transplant Congress.

Acute transplant rejection occurs when cells of the immune system recognize the transplanted organ as foreign and attack it as a potential threat. Powerful immune-suppressing drugs - including sirolimus - keep the immune system under wraps and prevent this immediate rejection.

Immune cells passing through blood vessels in the transplanted heart, however, inflict a consistent, low-level attack on cells lining the vessel walls. In response, these smooth-muscle cells build up scar tissue that may eventually block the vessel and starve the heart of oxygen. This process, called chronic rejection, is the most common cause of heart transplant failure. "To prevent chronic rejection, you want to stop proliferation of smooth-muscle cells," Morris said. His research shows that's exactly what sirolimus does.

Laying the groundwork

In studies during the late 1980s, Morris transplanted hearts in rats using sirolimus to prevent rejection. Not only did the rats avoid rejection problems, but the hearts that received sirolimus had muc
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Contact: Amy Adams
amyadams@stanford.edu
650-723-3900
Stanford University Medical Center
25-Apr-2002


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