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Cyclosporine: A Drug with Vast Promise

May 11, 1986

WASHINGTON (AP) _ A drug derived from a soil fungus found in southern Norway by a vacationing scientist in 1970, and almost written off as worthless at the time, is looming as perhaps the next miracle drug of the 20th century.

The drug is cyclosporine, and its effect is to suppress the body’s immune system. In organ transplants, the drug has doubled success rates by suppressing the body’s tendency to reject foreign organs.

Scientists exploring the drug are finding broader applications that hold potential for treating or preventing a number of serious diseases, including AIDS, diabetes, mutiple sclerosis and malaria.

And in more basic research, scientists say cyclosporine may hold the key to unlocking the secrets of how the immune system works, opening the door to even wider use.

″If you want to be really hard-nosed about it, you’d have to say it’s not a miracle drug″ because of potentially serious side effects, said Dr. Allan Hess, a cyclosporine researcher at Johns Hopkins Medical Institutions. ″But, boy, it’s one of the closest things we’ve got.″

The possible side effects include kidney damage and increased risk of lymphoma, a cancer of the immune system. Scientists are uncertain how a lifetime of taking the drug will affect the risk. But they note that the diseases being studied for cyclosporine use are extremely dangerous themselves.

Last week, French scientists told a scientific conference in Los Angeles that cyclosporine may prevent AIDS because it appeared to restore crucial cells in the damaged immune systems of eight of 16 patients who had evidence of AIDS virus infection but hadn’t developed the disease.

″We think it’s a very promising treatment″ for preventing such patients from developing acquired immune deficiency syndrome, said Dr. Jean-Marie Andrieu of Laennec Hospital in Paris.

Other scientists are exploring findings that cyclosporine may stop the progression of juvenile diabetes if it is given quickly enough, apparently by preventing the immune system from destroying the pancreas.

It also is being tested against myasthenia gravis, a degenerative muscle disease that afflicts as many as 100,000 Americans. In the disease, the body’s immune system attacks its own muscle tissue.

A National Institutes of Health researcher is testing cyclosporine to treat uveitis, an eye disease in which the immune system attacks eye tissue and causes blindness.

The initial successes against these immune-system diseases are prompting scientist to look at others, including multiple sclerosis.

There is evidence that cyclosporine may be effective against some kinds of leukemia. And scientists say initial tests also show cyclosporine appears to eliminate the body parasites that cause malaria and schistosomiasis, serious diseases that are rampant in the Third World.

But even if all of those research efforts fall short of scientists’ hopes, cyclosporine already has established its mark in the field of organ transplants.

By suppressing the body’s tendency to reject transplanted organs, it has doubled the success rates of some types of organ transplants and moved them from the experimental to the almost routine.

In kidney transplants, one-year survival rates jumped from about 50 percent to about 85 percent after the arrival of cyclosporine. Survival rates for liver transplants rose from 35 percent to 70 percent, and for heart transplants from 62 percent to 79 percent.

The Health Insurance Association of America has called cyclosporine ″the single most important factor in the dramatic rise in transplant procedures.″ The new success has prompted most insurance companies to cover heart and liver transplants.

And a federal task force has recommended that the federal government buy cyclosporine for elderly, poor Medicare patients undergoing transplants who otherwise might face death.

Little of this promise was apparent in 1970, when a vacationing microbiologist from Sandoz Ltd. of Switzerland took a sample of the soil in Hardanger, Norway, for routine tests.

The tests showed a previously unknown fungus that produced a metabolite called cyclosporine. Sandoz used a fermentation process to produce more of the metabolite, which was then tested as a possible antibiotic for fighting infection.

It was a failure. It then was tested as a possible cancer treatment. It failed again, and was shelved and almost forgotten.

But Dr. Jean F. Borel, an immunologist at Sandoz, was curious about the fungus and continued his own tests. In 1972, he discovered its immune system effects, and in 1978, the first tests in humans were conducted.

In 1983, the Food and Drug Administration approved the use of Sandimmune, Sandoz’ trade name for the drug, in transplant operations.

Cyclosporine is not without danger. It can have toxic effects on the kidneys, so its use must be monitored closely. However, the kidney effects, while serious, are usually reversible and can be controlled.

Patients receiving cyclosporine also have higher rates of lymphoma, a sometimes fatal cancer of the immune system. While the immediate risk of lymphoma is dropping as researchers gain experience with the drug, there is no way to know how a lifetime of treatment may affect the long-term risk of such serious complications, particularly among very young transplant patients.

Another side effect is not medical - the drug causes a sharp pain to the wallet.

Cyclosporine is horrendously expensive. A year’s supply for a transplant patient can run from $3,000 to $5,000, and it apparently must be taken for the rest of the patient’s life.

Sandoz Inc., the U.S. subsidiary of Sandoz Ltd., says it is trying to bring down the price, but it makes no predictions and offers no promises.

The problem is the production process. It is not made by mixing chemicals, a process that could be put on an assembly line, but by growing fungi.

The procedure is now done in room-sized tanks in Austria, and the extract from the fungi is purified at a Sandoz laboratory in Switzerland.

″It’s a fermentation process that is very time-consuming,″ said Blanche Higginbotham of Sandoz. ″We haven’t found an easy way yet.″

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