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
“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
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
- 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
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
Dr. William Clarke, University of Iowa (Data Coordinating Center)
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
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.
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
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)
assists translation to the clinic of novel therapeutic interventions
for type 1 diabetes and its complications.