The Science Behind the Cure
There’s been good news recently. Dramatic breakthroughs in the research and treatment of diabetes are offering new hope to millions of patients and their families.
Whole-pancreas transplantation has been very successful in restoring insulin production in patients with advanced diabetes. But the procedure has significant limitations. Because of the risks, it has been primarily available to those also undergoing kidney transplantation. And the long-term use of immunosuppressant drugs seriously compromises patients' ability to ward off even common infection and diseases. Moreover, the availability of organ donors is extremely limited, and this option is not available to children.
In 2000, clinical trials demonstrated that islet cells could be isolated, donated and transplanted, successfully triggering blood glucose sensing and regulated insulin production in most patients. It’s done on an outpatient basis, transfusing cells by catheter into the liver. But because islets make up only 1% to 2% of the pancreas, the procedure requires multiple donors for each transplant. Additionally, patients must take immunosuppressant drugs for the rest of their lives, risking harmful consequences. And the cost is prohibitive—about $100,000, with little third-party payment available. Thus, studies funded by National Institute of Health (NIH) grants limit participation to adults with the most advanced, complex cases of diabetes.
Dr. Bernhard Hering is a Scientific Director of the Diabetes Institute for Immunology & Transplantation and Director of the Islet Transplantation Program at the University of Minnesota. He is internationally recognized for his many contributions to islet transplantation. Recently, Dr. Hering led a clinical study of eight type 1 diabetic patients from 2001-2003, and reported the results in the February 2005 issue of the Journal of the American Medical Association. All eight achieved insulin independence and maintained superior glycemic control. Five patients remained insulin independent for more than a year, and even those with only partial islet function were able to normalize blood sugar levels with small doses of insulin. Severe hypoglycemic episodes were virtually eliminated. Plus, researchers were able to secure sufficient islet cells from just one donor per recipient instead of two to four. Still, the availability of donors severely constrains wide availability.
Dr. Hering continues to research the effects of transplantation on the immune system. Because antirejection drugs can dangerously elevate blood sugar levels, they can increase the metabolic demand on transplanted islet cells. As co-director of the NIH Immune Tolerance Network Islet Transplant Subgroup, Dr. Hering helped develop protocols to allow islet transplantation without continuous immunosuppression. So far, Dr. Hering’s research has resulted in the development of safer, more effective antirejection drugs, which are much less stressful to the cells—and the patient.
As promising as islet cell transplantation is, the limited number of donors remains a stubborn obstacle. Dr. Hering and the team at the University of Minnesota’s Diabetes Institute for Immunology and Transplantation hypothesized that islet cells from pigs could be developed into a widely available cell replacement therapy. To test their idea, they first developed safe and effective protocols to prevent tissue rejection and to secure a suitable source of pigs.
The Food and Drug Administration has stringent biosecurity rules for animal-to-human tissue transplantation that both minimize risks and the potential exposure to diseases. To address these issues, University of Minnesota scientist Scott Fahrenkrug, Ph.D. is developing pigs with islets not recognized as foreign by a patient’s immune system, as well as pigs incapable of transmitting porcine endogenous retrovirus to humans.
Enter Abraham the pig. Abraham was selected as the originator of source pigs because of superior genetics, health and breeding performance. His offspring are under the management of Hutterite farmers in South Dakota.
Pig islet cells were harvested and transplanted into twelve diabetic monkeys in University of Minnesota labs. Monkeys have immune systems remarkably similar to humans.
And it worked! Using immunosuppression protocols, the monkeys accepted the islet cells and began producing sufficient insulin to reverse their disease. This landmark research, a relevant preclinical trial, suggests that islets isolated from pigs can serve as an unlimited source of donor tissue to reverse diabetes.
Even better, instead of a lengthy surgery and recovery, an islet transplantation procedure involves a series of injections, each of which lasts about an hour and requires only a local anesthetic.
Additionally, the islet cells’ survival, function and immune tolerance can be manipulated and improved by scientists through animal genetics and transgenesis, eventually leading to a cure for diabetes patients that may not involve a regimen of immunosuppresants.
For more detailed information, see the statement from Dr. Hering, linked below.
