Two major enterprises toward successful islet transplantation were announced in October by the Juvenile Diabetes Foundation (JDF).
One program will link 40 islet research institutions around the world, to be known as the Collaborative Network for Clinical Research on Immune Tolerance. The JDF and two of the National Institutes of Health, the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases, will cosponsor this $144-million initiative, aimed at finding safer methods of immune tolerance, preventing the body’s rejection of transplanted organs. Along with islet transplants to cure diabetes, the network will study transplants to cure other immune system disorders like multiple sclerosis, lupus and arthritis.
Current transplant recipients must take immunosuppressive drugs that suppress the body’s immune system so that it will not attack and destroy the transplanted organ, as it attacks any foreign substance. The problem is that the entire immune system is turned off, leaving people susceptible to bacteria, viruses and cancer cells.
Network centers will conduct trials of “tolerogenic” drugs, which are hoped to be able to select immune cells to turn off, only shutting down the cells responsible for destroying the transplanted organ, not the ones that protect from other invaders.
The 39 centers are located all over the United States as well as in Australia, Germany, Canada and Italy. Likely leaders will be researchers at the University of Chicago and the University of Minnesota, who will lead the other major initiative announced by the JDF.
Chicago and Minnesota
Called the JDF Center for Islet Transplantation at the University of Chicago and the University of Minnesota, this grant recognizes the two schools’ strides in islet transplantation and gives them the go-ahead for improving on current work.
This center will also perform trials of tolerogenic therapies, but will deal only with islet transplants. The additional challenge in islet transplantation is to also stop the body’s autoimmune response that killed a person’s own islets, originally causing diabetes.
Chicago’s Jeffrey Bluestone, PhD, an immunobiologist, and Minnesota’s Bernhard Hering, MD, a world leader in the islet field (see page 36), will lead the center. Bluestone will use his immune response expertise to find a drug combination that will turn off both the immune and autoimmune responses after islet transplantation. Hering and his colleagues will try out genetically engineered antibodies in islet transplant patients. Two antibodies, anti-CD3 and anti-CD154, have succeeded in animals at preventing destruction of transplanted islets without leaving the animals open to infection. The center’s trials will test these two drugs in humans.