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David Sutherland

Since performing the world's first transplant of insulin-producing islet cells in 1974, David Sutherland has led the way in many other major achievements in diabetes research.

Closer and closer to a cure?

Latest research holds promise for reversing the most severe form of diabetes

By Mary Hoff

Dec. 5, 2006

Editor's note: This year marks the 40th anniversary of the world's first successful pancreas transplant. That triumph also marked the start of the U's pancreas transplant program, which is now the oldest and largest in the world. U surgeons have performed more than 1,500 pancreas transplants and that number continues to grow at a rate of 150 each year. We hope you can attend the two events this weekend--see sidebar--celebrating this special anniversary.

To the million or so Americans with Type 1 diabetes, the notion of one day being disease-free seems too good to be true. But, says David Sutherland, it could become a reality in the foreseeable future.

Sutherland directs the Diabetes Institute for Immunology and Transplantation, the University of Minnesota's focal point for research aimed at advancing the transplantation of insulin-producing islet cells to cure diabetes. Since it was founded in 1994, the institute has made great strides in refining whole-organ pancreas transplants and islet transplants to more effectively treat Type 1 diabetes. This past winter, associate director Bernhard Hering announced the results of a landmark study that moves researchers closer than ever to a possible cure: They successfully reversed diabetes in 12 monkeys by transplanting islet cells from pigs.

Brian Flanagan, acting director of the Juvenile Diabetes Research Foundation's islet biology and transplantation program, calls the report--along with one from an Emory University team also looking at pig islets--"milestones."

"We were very encouraged by those papers," Flanagan says. "It is a significant step forward. But we're certainly not at the end yet."

Devastating disease

Diabetes actually comprises several disorders. Their common thread is an inability to properly control the amount of glucose circulating in the blood.

Normally, when the digestive tract releases energy in the form of glucose into the body, beta cells--found in the pancreas in cell clusters called islets - release insulin. Just as a subway token admits riders through a turnstile, insulin ushers glucose into body cells, where it is used or stored for future energy needs.

In Type 1 diabetes, the kind that most commonly appears in childhood, a person's immune system mysteriously destroys his or her beta cells. Traditional treatment involves painstaking daily insulin shots, or infusion. Even with the best of care, many with Type 1 diabetes suffer devastating and sometimes deadly side effects, including kidney disease, circulatory problems, and blindness.

40th anniversary lectures

Face transplant
In November 2005 doctors in France performed the first partial face transplant, in which tissues, muscles, arteries and veins were taken from a brain-dead donor and attached to the patient's lower face. Jean-Michel Dubernard, who co-led the surgical team, will be keynote speaker at "The First Face Transplant: Medical, Ethical and Media Perspectives" on Thursday, Dec. 7, at 1:30 p.m. in Coffman Union's Great Hall on the Twin Cities campus. Discussion will follow with Gary Schwitzer, assistant professor in the School of Journalism and Mass Communication, and Jeffrey Kahn, director of the University of Minnesota's Center for Bioethics. To register for this event, visit the Academic Health Center.

Pancreas transplant symposium
On Dec. 8-9, "40 Years of Pancreas Transplantation: An International Collaboration" will feature pioneers in pancreas and islet transplantation from around the world. For more information or to register, visit the Medical School.

Why not replace the destroyed islets with ones that work? In 1966 University of Minnesota surgeons Richard C. Lillehei and William D. Kelly did just that when they performed the world's first pancreas transplant. Sutherland took the concept one step further in 1974 when he transplanted islets from a deceased donor into a patient with diabetes.

But there are hefty obstacles to overcome before islet transplantation can be considered a viable cure. A major one is improving the effectiveness and reducing the adverse effects of the immunosuppressive drugs used to prevent the recipient's body from rejecting the foreign cells. Another is figuring out how to provide enough islets to meet the demand. Each year about 30,000 Americans are diagnosed with Type 1 diabetes, while only about 6,000 donor pancreases become available.

When Sutherland and his colleagues established the Diabetes Institute for Immunology and Transplantation in 1994, it was to initiate a full-court press against these obstacles. Two years later, Hering, a renowned leader in islet transplant therapy, joined them.

"We need to have this mindset that diabetes is a curable disease, and we should not accept anything else that will not get us there; anything else will be a compromise," says Hering, who holds the Eunice L. Dwan Diabetes Research Chair. "I know it is possible."

In the years since then, the institute has made substantial progress. By developing, testing, and refining various approaches to harvesting and handling islets and preventing rejection, institute staff have been able in clinical trials to reverse diabetes in some islet recipients for years.

Institute staff has stretched the islet supply as well. Last year Hering reported success using islets from a single donor, rather than the two or more normally required. But the availability of islets still remains a serious limiting factor.

"The real advantage of islets is to come in the future, when we can get islets from another source," Sutherland says.

"We need to have this mindset that diabetes is a curable disease, and we should not accept anything else that will not get us there; anything else will be a compromise," says Hering, who holds the Eunice L. Dwan Diabetes Research Chair at the U. "I know it is possible."

One step away

Having successfully transplanted pig islets into monkeys, the researchers are eager to develop a safe, effective protocol for doing the same in humans.

"There's a lot of momentum to position us to expedite and lead the development of pig islets to potentially benefit people with diabetes," Hering says. "This is one step away for us. The question is: How long will that step be?"

Before pig islet transplantation can enter clinical trials, the researchers must conduct additional studies - based on what they've learned about how the monkeys' immune systems reacted to the pig islets--to identify an antirejection strategy for humans. They also must find a way to raise pigs under the stringent conditions required by the U.S. Food and Drug Administration for producing tissue for use in humans.

"We have both initiatives well under way," Hering says. The institute has recruited several additional researchers to carry the antirejection work forward. It is also looking at novel approaches, such as placing islets and antirejection drugs together under the skin or in abdominal fat to avoid the adverse effects of full-body immune suppression.

Bernhard Hering
U researcher Bernhard Hering led a study that reversed diabetes in 12 monkeys using islets transplanted from pigs.

While researchers continue their work, a separate nonprofit organization, Spring Point Project, is working to fund and build a facility for raising the pigs needed to produce islets. The researchers hope to receive FDA approval to start the clinical trial phase in three years, with the first pig islets implanted in humans within about five years.

"At some point in the hopefully not-too-distant future, people with diabetes will have better options available to them," Hering says. "They will be able to get a pig islet transplant without toxic immune suppression and enjoy the beauty of life free of diabetes."

As he looks forward to further advances, Hering also expresses gratitude to the donors who made it all possible by investing in exploratory research.

"If we had gone with the initial idea [of pig islet cells] to major funding organizations, they would have said, 'Now you have gone completely insane,'" says Hering. "That's why you need philanthropic donations."

Republished from Medical Bulletin, spring 2006, a publication by the Minnesota Medical Foundation.