A Heart-Saving Gift from Easter Island

Sirolimus looks like wonder drug for people who have heart transplants

FRIDAY, May 3, 2002 (HealthDayNews) -- It started out as an ineffective anti-fungal medication created from some Easter Island bacteria, but sirolimus is proving itself a wonder drug for people who have had heart transplants.

Used since 1999 to prevent rejection of transplanted organs, researchers now believe sirolimus can protect the blood vessels of transplanted hearts -- the leading cause of heart transplant failure.

Transplant rejection happens when the body's immune system recognizes the transplanted organ as foreign and attacks it. A number of drugs, including sirolimus, have been developed to stop this primary rejection.

However, the body's attempts to reject the organ causes damage to the blood vessels leading to the heart. Over time, the vessels build up scar tissue that could eventually block the vessels and starve the heart of oxygen.

Dr. Randall Morris of Stanford University has a primate study in hand that shows the same process that makes sirolimus a good immune suppressant also keeps the heart's blood vessels clean.

The drug works by blocking hormonal signals to immune cells, preventing them from receiving the word to attack the transplanted organ. Morris finds the drug also blocks hormonal signals to scar tissue cells.

"It has this sort of dual action that the other immunosuppressive drugs do not," he says.

Morris conducted an experiment in which he transplanted aortas -- the major artery leaving the heart -- between 12 monkeys. Half the monkeys received treatments of sirolimus, and half did not.

After 105 days, the animals receiving sirolimus had arteries that were nearly normal, while the aortas of the other monkeys were significantly clogged, Morris says.

The maker of the drug, Wyeth-Amherst Laboratories, already has performed one human trial in Australia to test its usefulness in preventing arterial disease in transplant patients, says Dr. Joseph Camardo, the company's senior vice president for clinical research and development.

About 200 patients were given sirolimus following coronary artery grafts or heart transplants.

"It turned out after six months, you could see a significant difference," Camardo says. "Sirolimus appears to prevent or at least slow down coronary vascular disease."

Camardo says the company has yet to apply to the U.S. Food and Drug Administration (FDA) for permission to use sirolimus in heart transplant patients because research on the drug's possibilities is continuing.

Sirolimus' odyssey from Easter Island to America's hospitals began with a Canadian geologic survey in the 1960s that led to the discovery of unusual bacteria in a soil of the South Pacific island.

Wyeth-Amherst developed the bacteria into sirolimus, which the company thought might prove a good anti-bacterial or anti-fungal treatment. However, those uses were ineffective in early trials and the drug was shelved.

In the late 1980s, however, researchers, including Morris, realized sirolimus had a chemical structure very similar to another drug being tested as a potential immune suppressant.

Morris and others tested sirolimus, and found it kept the immune system from attacking transplanted organs without many of the toxic side effects found in other drugs.

"We sort of did the right thing for the wrong reason," Morris says.

The drug, marketed under the trade name Rapamune, was approved by the FDA for use on transplant patients in 1999.

Researchers have since found sirolimus also helps patients who have undergone angioplasty, a procedure in which cardiologists use balloons to open clogged arteries. To keep the arteries open, the doctors insert coiled wires called stents. However, they found scar tissue would eventually build up around the stents, blocking blood flow.

Cardiologists experimented by implanting stents coated with sirolimus. Two years later, they found the blood vessels were still clear.

What To Do: To learn more about sirolimus, visit the National Library of Medicine. For more information on heart transplants, go to the American Heart Association.

SOURCES: Randall Morris, head, Transplantation Research Laboratories, Cardiothoracic Surgery, Stanford University, Palo Alto, Calif.; Joseph Camardo, M.D., senior vice president, clinical research and development, Wyeth-Amherst Laboratories, York, Pa.
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