NIH funds centers to study islet transplantation
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."
Researchers in the newly funded centers will be designing studies to:
- improve the isolation and viability of islets
- reduce complications of the transplant procedure, e.g., bleeding and clotting
- reduce the side effects of immunosuppression
- trace the fate of islets after transplantation and determine why donor islets sometimes fail
- evaluate new ways to safely prevent immune rejection of donor tissues.
Newly designed studies will be submitted for review by the Food and Drug Administration, the NIDDK/NIAID Islet Transplantation Data and Safety Monitoring Board, and local institutional review boards before being offered to patients. Patient enrollment is scheduled to begin in 2005.
The consortium consists of the following principal investigators and centers:
Dr. William Clarke, University of Iowa (Data Coordinating Center)The consortium is supported by a special funding program for type 1 diabetes research, which provides a total of $1.14 billion from fiscal year 1998 through fiscal year 2008 to supplement other funds for type 1 diabetes research made available through the regular NIH appropriations process.
Iowa City, Iowa
Dr. Camillo Ricordi, University of Miami
Dr. Bernhard Hering, University of Minnesota
Dr. Ali Naji, University of Pennsylvania
Dr. James Shapiro, University of Alberta
Edmonton, Alberta, Canada
Dr. Olle Korsgren, Uppsala University
Other NIH-funded initiatives are also fostering progress in islet transplantation. The Collaborative Islet Transplant Registry [http://www.nih.gov/news/pr/sep2004/niddk-07.htm], which recently published its first annual report, collects, analyzes, and disseminates data on islet transplants performed in the United States and Canada. Ten Islet Cell Resource Centers [ http://www.ncrr.nih.gov/clinical/cr_icr.asp ] harvest, purify, and ship islets for transplantation and research. The Immune Tolerance Network [www.immunetolerance.org] is an international consortium dedicated to evaluating new treatments for autoimmune diseases, asthma, and allergic diseases, and to preventing the rejection of transplanted organs and islets. The Beta Cell Biology Consortium [www.betacell.org] facilitates interdisciplinary efforts to understand islet development and function. The Non-Human Primate Islet Transplantation Consortium develops and tests new protocols for immune suppression in transplant recipients before these protocols are tested in patients. In addition, the Type 1 Rapid Access to Interventional Development program (T1-RAID) [http://www.niddk.nih.gov/fund/diabetesspecialfunds/T1D-RAID/ ] assists translation to the clinic of novel therapeutic interventions for type 1 diabetes and its complications.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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