$75 million over 5 years to study islet transplantation in patients with type 1 diabetes

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The National Institutes of Health (NIH) announced today that it plans to award about $75 million over five years to five clinical centers and a data coordinating center to conduct studies of islet transplantation in patients with type 1 diabetes.

The network includes centers located in Iowa City, Miami, Minneapolis and Philadelphia, as well as in Edmonton, Canada, and Uppsala, Sweden.

The studies will focus on improving the safety and long-term success of methods for transplanting islets, the insulin-producing cells of the pancreas, in people whose own islets have been destroyed by the autoimmune process that characterizes type 1 diabetes. Some studies will focus on improving combined islet and kidney transplants in patients with type 1 diabetes and kidney failure, a common complication of diabetes.

“This award accelerates studies of an experimental approach that could be very promising for some people with severe type 1 diabetes if specific barriers can be overcome,” said Dr. Thomas Eggerman, who oversees the consortium for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Two institutes of the National Institutes of Health (NIH)--the NIDDK and the National Institute of Allergy and Infectious Diseases (NIAID)--sponsor the consortium.

Type 1 diabetes accounts for up to 10 percent of diagnosed cases of diabetes in the United States (up to 1 million people). This form of diabetes usually strikes children and young adults, who need several insulin injections a day or an insulin pump to survive. Insulin, though critical for controlling blood glucose, is no cure. Most people with type 1 diabetes eventually develop one or more complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys.

In islet transplantation, islets are extracted from the pancreas of a deceased donor and infused into a person with difficult-to-control type 1 diabetes though the portal vein of the liver. In successful transplants, the cells lodge in the liver’s small blood vessels and begin producing insulin.

In the 1990’s, islet transplantation rarely succeeded in freeing patients from insulin injections for more than a year. In June 2000, however, a research team led by Dr. James Shapiro at the University of Alberta in Edmonton, Canada, reported sustained insulin independence in seven patients transplanted with islets from two to four donor pancreases. The patients received an immunosuppressive regimen that omitted glucocorticoids, also known as steroids, which were often used to prevent rejection but are now thought to be toxic to islets. In the next few years, researchers participating in the Immune Tolerance Network (ITN), a collaboration of clinical and basic researchers sponsored by the NIAID, NIDDK, and the Juvenile Diabetes Research Foundation International, replicated what became known as the “Edmonton protocol.”

Despite these gains, scientists continue to grapple with several impediments to the wider testing of islet transplantation. One is the scarcity of islets. Only about 6,000 donor pancreases become available each year, and many are used for whole organ transplantation. Posing another obstacle are the potentially serious side effects--such as anemia, nerve damage, meningitis, and vulnerability to infection--of the medications that stop the immune system from rejecting donor islets. Finally, in some transplanted patients, donor islets function well initially, but in time diabetes recurs. Why the islets die is not well understood.

Recent NIH-funded advances may lead to some answers. “Newly developed immune assays are helping us flesh out a more complete picture of the immune events that trigger rejection,” said Dr. Nancy Bridges, who oversees the consortium for NIAID. “Studies are also laying the groundwork for less toxic immunosuppressive agents, which will be tested in upcoming trials. Our ultimate goal is to develop ways to induce tolerance, a state of immune acceptance of the donor tissue or organ.”


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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