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

h cleaner blood vessels than those that received a different anti-rejection drug. "We thought maybe sirolimus did more than just suppress the recipient immune system," Morris said. "Maybe it also acted on donor blood vessels."

These results inspired Morris and postdoctoral fellow Camille Dambrin, MD, to test sirolimus on transplanted aortas - the major artery leaving the heart. In their initial trials on rats and primates, delayed treatment with sirolimus stopped the progression of chronic rejection once it had started. In the latest work, the researchers tested whether sirolimus could prevent chronic rejection altogether if the drug was started at the time of transplant.

They transplanted aortas in 12 primates: six received sirolimus throughout the trial while six received a placebo. They monitored the internal diameter of the transplanted vessels with ultrasound for 105 days. The animals that received sirolimus had arteries that were nearly normal compared to the significantly clogged arteries in animals that had received the placebo.

Morris said early results from this work led to the use of sirolimus to prevent chronic rejection in human heart transplants. The federal Food and Drug Administration approved the drug for use by transplant recipients in 1999. He added that worldwide trials in human heart transplant recipients using sirolimus or a chemically modified version show these drugs significantly prevent artery narrowing.

Another notable application

While preventing chronic rejection would be a major improvement for heart transplant patients, the most significant use of sirolimus may address a different problem. Cardiologists often use balloons to open clogged arteries in a process called angioplasty. They then insert coiled wires called stents to hold the artery open. Scar tissue can eventually build up around the stent, blocking blood flow.

In recent trials, car
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Contact: Amy Adams
amyadams@stanford.edu
650-723-3900
Stanford University Medical Center
25-Apr-2002


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