Originally created 05/20/00

New cell transplant offers promise



WASHINGTON - Eight adults with severe diabetes were able to quit their insulin shots after Canadian scientists tried a new technique in transplanting insulin-producing pancreas cells.

It's too soon to know how long the effect will last, but the experiment is generating cautious excitement that these long hoped-for transplants could finally work.

"The fact that they have those eight consecutive patients insulin independent is unprecedented," said Dr. David Harlan, diabetes transplant chief at the National Institutes of Health, which hopes to help test the new technique. "This is a very compelling story."

Within months, the Canadian scientists plan to begin another study at eight hospitals, including some in the United States, to perform at least 32 additional cell transplants, a step toward proving they can work.

Some 1 million Americans have Type 1 diabetes, also called juvenile diabetes even though people of any age can get it. Patients' immune systems destroy pancreatic cells that secrete insulin, a hormone crucial to converting sugar into energy.

Type 1 diabetics need regular insulin shots to survive. Despite that treatment, many patients ultimately go blind, develop kidney failure or suffer other life-threatening complications.

Diabetics who get kidney transplants sometimes receive pancreas transplants at the same time, and the new pancreas can reverse diabetes. But it's a rare and grueling operation, so scientists for years have hoped instead to inject diabetics with islet cells, the insulin factories inside the pancreas.

Until now, "the results have been dismal," said Dr. James Shapiro of the University of Alberta. Fewer than 1 in 10 islet-transplanted patients have been insulin-free a year later.

So Shapiro's transplant team in Edmonton, Canada, tried a new technique. All eight transplant recipients so far have normal blood sugar without taking any insulin, he reported this week at meetings of transplant surgeons and the Juvenile Diabetes Association.

Before the transplants, these patients' diabetes raged despite maximum insulin doses. One woman took 15 insulin shots a day yet still had uncontrolled blood sugar.

The first patient transplanted has lasted 14 months without needing insulin, and half the patients have lasted almost a year. Shapiro said none shows signs of rejecting the cells or serious side effects from the transplant - which merely required an injection, not surgery.

Eight patients aren't enough to prove this will work, cautioned the NIH's Harlan. Nor does anyone know long-term effects. The next experiments will be only for worst-case patients.

"As excited as I am, and everyone is, about these data, we have to understand we don't know a lot yet," Harlan said.

Shapiro made a number of changes to standard islet transplants. The most important:

-He didn't give patients steroids, which transplant recipients commonly use to keep their immune systems from attacking transplanted cells or organs.

Islet-cell recipients will need immune suppression for the rest of their lives. But Shapiro said animal studies suggest steroids are toxic to islet cells, so instead of a steroid he substituted a new genetically engineered anti-rejection drug called Zenapax.

-He used islet-cell doses far higher than ever tried. A normal pancreas has almost 1 million islet cells, yet surgeons have been unable to cull more than half that number from donated pancreases. So Shapiro used two pancreases to get enough.

That's a problem, because only a few thousand pancreases are donated in this country every year. Thus, if the transplants ultimately work, there would be a shortage.

And Shapiro cautions that questions about the long-term effects of immunosuppressants means islet transplants for now will be tested only in adults, not children.

Within a few months, a network funded by the NIH and Juvenile Diabetes Foundation will name the eight hospitals that will participate in the new transplant study.

On the Net:

Juvenile Diabetes Foundation International: http://www.jdf.org/research/news051900.html