Islet Transplantation: A JDRF Success Story

The restoration of euglycemia (normal blood sugar) in people with Type 1
diabetes has been the ultimate goal of researchers for more than 30
years. In recent years, islet cell transplantation has emerged as the
most promising option for achieving euglycemia. With remarkable
foresight and determination, JDRF has shepherded this procedure from a
field marked by disappointment and frustration to one of tremendous
promise.\
\
With islet transplantation always high on JDRF\'s research agenda, its
investment began paying off dramatically in 2000 with the success of the
\"Edmonton Protocol\" at the University of Alberta in Canada. The
protocol \-- transplanting insulin-producing islets into diabetic
patients with less toxic immunosuppressive drug therapy \-- was quickly
hailed around the world as a major transplantation breakthrough, a major
scientific \"proof of principle,\" and the start of a JDRF-led
accelerated effort to replicate and improve on this achievement.\
\
**Laying the Groundwork**\
JDRF funding had established the groundwork for the success of islet
transplantation many years earlier, when in 1976 one of JDRF\'s earliest
research grant recipients, Paul E. Lacy, M.D., Ph.D., at Washington
University School of Medicine, performed the first successful islet
transplantation in diabetic animal models. Over the next quarter
century, researchers \-- on the same decades-long learning curve as that
of whole organ transplantation \-- struggled to reproduce the procedure
successfully in humans.\
\
One of the first such attempts was funded by JDRF in 1982, with other
experimental trials continuing through the decade and into the 1990s,
but with success rates \-- defined by the achievement of independence
from the need for insulin injections for a sustained period \-- always
remaining under 10 percent. A major hurdle, overcome with help from JDRF
funding, was making sufficient numbers of islets available for research.
JDRF-funded research also produced advancements in transplant
techniques, understanding of the immune system, and refinements in
immunosuppression, which would pave the way for Edmonton and other
important successes of the last two years.\
\
**Elevating Islet Transplantation on the International Agenda**\
In the mid 1990s, with islet transplantation poised for a breakthrough,
JDRF once again led the way \-- anticipating where the science was
going, directing funds to the right area, and attracting leading
scientists to the field. In 1997, JDRF\'s Task Force I elevated islet
transplantation to the level of an international initiative by setting
the following goals:

-   Overcome the remaining problems of immune tolerance and immune
    rejection

-   Jump-start human clinical trials

-   Address the shortage of available islets

-   Establish the infrastructure for the isolation and distribution of
    islets for research

As the centerpiece of this initiative, JDRF called for the establishment
of interdisciplinary science-with-a-mission JDRF Research Centers,
culminating in an historic launch: In 1998, the JDRF Center for Islet
Transplantation at Harvard Medical School became the first such
institution devoted to the single purpose of finding a cure for diabetes
through islet transplantation.\
\
Also in 1998, to fulfill the goal of making islets available, JDRF
launched the JDRF Human Islet Distribution Programs, which ensured a
steady supply of high-quality islets for research and helped make the
Edmonton Protocol possible.\
\
\"We saw the promise of islet transplantation and realized more needed
to be done to make islets available for clinical studies,\" said Robert
Goldstein, M.D., Ph.D., Chief Scientific Officer at JDRF. \"Without an
ample supply of this resource, islet transplantation could not have
moved nearly so fast.\"\
\
In June 2000, after years of significant JDRF funding, the researchers
at the University of Alberta at Edmonton announced the success of their
new protocol. In an article published in the British journal *The
Lancet* (December 2001), James Shapiro, M.D., Ph.D., who developed and
led the team that implemented the protocol, reports about the first set
of patients: \"Of the 17 treated under the Edmonton Protocol, 85 percent
remain insulin free at one year, and 80 percent are still free of
insulin beyond two years.\"\
\
**Expanding on Success**\
Since June 2000, JDRF has put in place the mechanisms to quickly
disseminate and expand the Edmonton success. In the fall of 2000, the
[Immune Tolerance Network (ITN)](http://128.218.179.235/frameset.html)
was established, a seven-year \$144 million project co-funded by JDRF
and the NIH, devoted to research that leads to tolerance of transplanted
tissue and prevention of autoimmune conditions. The first major trial
supported by the ITN is a multi-center trial to validate the Edmonton
Protocol. Other ITN trials are scheduled, and now more than 20 research
centers around the world are working on a compressed timetable to
replicate the Edmonton Protocol success and test still newer promising
protocols.\
\
For example, a team at the JDRF Center for Islet Transplantation at the
University of Minnesota/University of California, San Francisco,
recently succeeded in successfully transplanting patients with islets
from only one donor pancreas, instead of the two required by the
Edmonton Protocol; other centers are reporting advancements in several
areas. The hope: Hastening these improvements will transform successful
transplantation into a routine procedure \-- and a cure.\
\
**Proceeding on Multiple Fronts**\
JDRF is working on scientific and advocacy fronts to ensure continued
success in islet transplantation and positioning the foundation to
continue to lead the way in hastening the pace of this research and
making it available to patients as quickly as possible.\
\
**Scientific:** As a result of recommendations by its 2001 Task Force
III, JFRF has concluded that it should adopt a research portfolio with
67 percent of its total investment provided for Goal Area #1,
restoration of euglycemia, with an emphasis on islet transplantation.\
\
Since 1998, JDRF has launched six more JDRF Centers for Islet
Transplantation including a new Center at the University of Alberta,
directed by Dr. Shapiro. JDRF has also helped increase the number of
islet resource centers to a total of 13 in the U.S. and around the
world. All told, JDRF funds islet distribution or transplantation at 28
sites around the world, either solely or in collaboration with the
National Institutes of Health (NIH).\
\
In addition to its support of islet transplantation research, JDRF has
begun an effort to increase the number of pancreata available for islet
transplants, as well as to establish a Medicare clinical investigation
on islet transplantation for people with juvenile diabetes and kidney
failure. JDRF is also in communication with the Food and Drug
Administration (FDA), which regulates all experimental therapies like
islet transplantation, to facilitate the path to approval of this
procedure to become a clinically accepted standard-of-care treatment.

**New Islet Sources** Perhaps most important, JDRF has led the way in
addressing the biggest remaining hurdle to transplantation \-- the
severe shortage of available islets. Even if organ donation were
maximized, it would help only a small number of the more than one
million people who have Type 1 diabetes in the U.S. alone.\
\
JDRF\'s Task Force II (2000) and Task Force III (2001) identified stem
cell research as a priority area and a key to a cure for diabetes and
many other crippling diseases. As a result, JDRF-funded researchers are
now pursuing the goal of coaxing human stem cells to change into
insulin-producing beta cells that then could be transplanted. At the
same time, JDRF continues to fund research employing other methods of
obtaining more islet cells; in the next fiscal year, the foundation is
planning a \$20 million increase in its investment to find new islet
sources.\
\
JDRF has also been the leader \-- both in Washington and across the
country \-- in advocacy efforts to ensure that federal funds are
available for stem cell research. In the last two years, the combined
voices of JDRF across the country significantly impacted public opinion
and national policy. To help advance the position, JDRF in 2000 helped
create the Coalition for the Advancement of Medical Research, an
organization that is providing a single strong voice on the issue for 50
national groups.\
\
**JDRF\'s Steadfast Support**\
With the scientific infrastructure in place and the research progressing
quickly, JDRF remains strongly committed to doing everything possible to
make islet transplantation medically successful and financially
affordable. JDRF will sustain the top islet transplant scientists with
the funds and support they require, and JDRF representatives and
volunteers across the U.S. will continue to play a prominent role in
influencing public policy.

Currently, islet transplantation is at a point where FDA involvement is
critical for the advancement of the procedure. JDRF urges the FDA to
consider the scientific and ethical benefits of making islet
transplantation a clinically accepted treatment and to begin to grant
licenses for this therapy in a timely manner.

\"Islet transplantation offers true promise as a cure for Type 1
diabetes,\" says JDRF President and CEO Peter Van Etten. \"JDRF support
has been instrumental to this field from the very beginning and at every
critical step. We will continue doing what is necessary to speed the
research so the scientists can reach their goal.\"