NEW DRUG MAY MAKE ISLET TRANSPLANTS A REALITY

Type 1 diabetes is caused by a failure of the islet cells of the human pancreas. When they perish, insulin is no longer produced in the body, and must be injected. For years, researchers have sought ways to restore the insulin-producing function to the pancreas, and thus eliminate the need for insulin injections.

The problem has always been immune rejection, the body's tendency to search out and destroy any foreign substance. We need this reflex, to keep us safe from infections and diseases, but it makes organ transplantation very difficult; and up to now has prevented successful transplantation of pancreatic islet cells. There are signs that may change.

A new study conducted by the Diabetes Research Institute at the University of Miami reports that the experimental anti-rejection drug anti-CD154 (hu5c8) has shown promise in animal research. In press at Proceedings of the National Academy of Sciences, the study reports that six diabetic monkeys were given this drug along with a transplant of islet cells. In all six cases, the recipients became insulin-independent. In three of the six cases, the animals remained insulin-free after discontinuing therapy one year after transplant.

The problem with immunosuppression, with using medications to suppress the body's normal defensive "immune response," is that it can make the patient vulnerable to diseases and infections, and in high doses can cause toxic side effects. (Also, current immunosuppressants have been insufficient to allow islet cell transplantation.) Anti-CD154 worked, and the study reports none of the animals experienced side effects from the drug.

Although this initial animal study is small, its implications could be far-reaching. "It's been the Holy Grail of islet cell transplantation to identify a safe anti-rejection agent that works in a diabetes model that is closer to human beings than a mouse," explains Norma S. Kenyon, PhD, associate professor of medicine, the study's lead author. "Anti-CD154 is an immune system modulator that prevents rejection without harming islet cells, and seemingly, without stunting growth or causing infection like traditional immunosuppressive agents. As a transplant immunologist who's worked in this field for almost 20 years, this is the most exciting development I've seen in a long time. However, as the mother of a daughter with diabetes, I don't want to raise false hopes."

So what has been accomplished? Dr. Kenyon and her colleagues have identified a new anti-rejection drug, and have used it to perform successful islet cell transplants in animals. If all goes well, there will be larger animal studies, then tests with human volunteers. If all stages prove successful, we may well see both a new and effective anti-rejection drug and the opportunity for simple, successful islet cell transplants, effectively curing type 1 diabetes. There are many hurdles to jump; it will take time; but there is now new hope.

For further information about this study, see the June 4, 1999 issue of Science magazine, or the following website: http://www.drinet.org