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Old drug shows new hope for transplants 4-30-02 UPI Science News
WASHINGTON (UPI) -- A once-obscure natural antibiotic found on a remote pacific island 30 years ago has re-emerged to assist long-term treatment of organ transplant patients, researchers reported Tuesday. Stanford University studies indicate the drug, sirolimus, controls the immune response of the organ recipient while also preventing arterial damage to the donor organ. This one-two punch effect makes sirolimus an ideal drug for treating heart transplant patients. 

Typical transplant procedures are complicated by the recipient's immune response to the alien organ. The donor heart comes under constant attack, causing its vessels to clog up with scar tissue. This response, known as chronic rejection, eventually closes off the vessels and prevents blood flow to the heart. Starved of oxygen, the heart dies.

"To prevent chronic rejection, you want to stop proliferation of smooth-muscle cells," said Dr. Randall Morris, who presented the research at the American Transplant Congress. "What's unique about this drug is that it blocks the replication of immune cells in the recipient but it also blocks the multiplication of scar tissue cells in the arteries which would lead to blockage of blood flow and the death of the organ," Morris added.

The Stanford team investigated whether the drug could prevent narrowing of the arteries in heart vessel transplants from one monkey to another. They took segments of arteries from twelve monkeys and grafted them into the aortas of twelve counterparts. After the procedure, six of the primates were treated with sirolimus while the rest were not. 

Dr. Morris' group measured arterial diameters every two weeks using a catheter to access the grafts and ultrasound technology to image the physical changes in artery size. The results showed that sirolimus was remarkably effective in both preventing the immune system from attacking the grafted arteries and in shutting down replication of scar tissue cells. "The drug prevented narrowing of the vessel completely but with the control group there was very significant narrowing (of the vessel) as we might expect," Morris said. 

Although sirolimus has been approved by the Food & Drug Administration to treat acute rejection in kidney transplant patients, it has yet to be endorsed for other transplant procedures. Dr. Morris' data suggest, however, the drug could be used for many different kinds of transplant procedures.

For several decades after its discovery on Easter Island, sirolimus languished on the laboratory shelf when initial studies failed to prove its effectiveness as an anti-fungal agent. Now, the drug is showing the potential to treat a wide range of complicated conditions and is generating excitement in many different fields of research. "The beauty of this drug is that it doesn't kill the cells it gets in contact with. It halts the cells and doesn't let them proliferate. It's a very smart drug and very well chosen," said Dr. Emerson Perin, cardiologist at St. Lukes Episcopal Hospital in Houston, Texas.

Sirolimus also is proving to be a powerful tool for combating a common artery repair complication. European and American researchers have found that stents -- tiny props used to repair damaged arteries -- can be impregnated with sirolimus to prevent scar tissue from forming in the artery after the repair procedure. The finding could be potentially revolutionary in the treatment of coronary artery disease using stents, a now widely adopted therapy received by a half million Americans every year -- including Vice President Dick Cheney.