Progress Seen in Transplants for Diabetes

This article from the New York Times was distributed via e-mail on Feb. 16, 2005 by the JDRF. We post it here for private educational purposes only.

The New York Times
Wednesday, February 16, 2005

By MARY DUENWALD

Doctors may have found a way around a major obstacle in the effort to perfect transplants of islet cells, an experimental treatment for Type 1 diabetes, a severe form that often begins in childhood.

Such transplants usually succeed only if islet cells from the pancreases of two or even three donors are used - a significant drawback, given the scarcity of donor organs. But now, in a trial of eight patients at the University of Minnesota, in Minneapolis, doctors have managed successful transplants of islet cells, which are needed to produce insulin, with the pancreases of single donors.

The use of anti-inflammatory drugs that are normally used to treat arthritis seems to have enabled many more of the transplanted cells to survive, said Dr. Bernhard J. Hering, director of the islet transplant program at the University of Minnesota. Patients were given these drugs before surgery to dampen the inflammation that otherwise destroys as many as half of transplanted islet cells in the first 24 hours, Dr. Hering said.

The doctors also cultured the donated islet cells in the laboratory for two days, rather than transplanting them within hours of isolating them from the donor pancreas. This step appears to give the islet cells greater resilience, Dr. Hering said.

The results of the trial are reported today in The Journal of the American Medical Association.

"This is really a long-awaited development, if it can be reproduced, because it means that the efficiency of islet cells is being increased," said Dr. R. Paul Robertson, scientific director of the Pacific Northwest Research Institute, a diabetes research center in Seattle. Dr. Robertson was not involved in the trial.

Diabetes researchers hope islet-cell transplants, which can be done almost as easily as a blood transfusion, in less than an hour, will one day free many people with Type 1 diabetes from the need to inject themselves with insulin several times a day to control their blood sugar.

But refining the procedure has not been easy. Among the first patients to have successful transplants five years ago, most are using insulin again-though not as much as they needed before their transplants.

Type 1 diabetes, sometimes called juvenile diabetes, occurs when the body's immune system destroys the insulin-producing cells in the pancreas, which are contained in tiny structures called the islets of Langerhans.

An estimated one million people in the United States have Type 1 diabetes.

Although it is possible to transplant the entire pancreas, the risk of death is great enough that the operation is rarely done in people who do not also need a kidney transplant because of diabetes-related kidney failure. Islet-cell transplants are less invasive and less dangerous.

Islet cells, which make up about 2 percent of the pancreas, can be isolated from cadaver pancreases and then transplanted through a catheter into the recipient's liver. They cannot be placed into the pancreas, because that organ is too vulnerable to inflammation.

When islet-cell transplants were first performed in humans, in the 1980's, they were rarely successful. But five years ago, surgeons at the University of Alberta in Edmonton adjusted the combination of immunity-suppressing drugs that are used to prevent rejection of the new cells and achieved successful transplants in eight patients.

Since then, the Edmonton protocol, with some variations, has been used on about 500 patients worldwide, said Dr. James Shapiro, director of the islet-cell transplant program at the University of Alberta, who designed the protocol.

"We've come a long way in a really short time, and I think islet transplantation is here to stay," Dr. Shapiro said. "It's still far from perfect, however."

A total of 73 patients have now received islet-cell transplants in Edmonton, most of whom have had the procedure twice. One year after transplant, 82 percent of patients need no insulin injections. After three years, however, that number falls to about 50 percent, Dr. Shapiro said. But after five years, he said, it appears that only 15 percent will still be independent of insulin.

"It appears that some of the grafts are failing, but it is not a complete failure," Dr. Shapiro said. "Some of the transplanted cells are still producing insulin."
Some of the cells may succumb to the anti-rejection drugs. Or perhaps the autoimmune reaction that caused the patient's diabetes kills them, Dr. Shapiro said.

Last month, working with surgeons in Kyoto, Japan, Dr. Shapiro accomplished the first islet-cell transplant from a living donor. A 27-year-old woman with Type 1 diabetes was given islet cells that had been isolated from half of her mother's pancreas.

Such transplants would expand the supply of donor cells. But some experts are wary of risks to donors.