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) 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."