Bluestone to head two new research projects

Major grants to support work in immunology, diabetes, transplants

At a campus press briefing yesterday, the Juvenile Diabetes Foundation and the National Institute of Allergy and Infectious Diseases announced two major, closely related, multiyear grants for research teams headquartered at the University.

The JDF has awarded $7.5 million over a five-year period to establish the JDF Center for Islet Transplantation at the University of Chicago/University of Minnesota. The NIAID has launched a seven-year, $144-million initiative involving nearly 40 research institutions that will be known as the Collaborative Network for Clinical Research on Immune Tolerance.

Both projects will be directed by Jeffrey Bluestone, the Daniel K. Ludwig Professor in Pathology, Chairman of the Committee on Immunology and Director of the Ben May Institute for Cancer Research at Chicago.

The JDF Center for Islet Transplantation, made possible by generous support from the McDonough Family Foundation in Chicago, will advance the transplantation of insulin-producing pancreatic islets as a cure for diabetes. It will focus on finding new ways to prevent the body from rejecting islet transplants without causing dangerous side effects.

The Collaborative Network will concentrate on developing and testing new ways to induce immune tolerance by selectively modulating the immune system to inhibit harmful responses and keep protective ones intact. This strategy promises to improve the success of transplants as well as treatments for autoimmune diseases such as type 1 diabetes, lupus and rheumatoid arthritis, which destroy the body’s cells.

“These are two vitally important, far-reaching and daring projects, and we are pleased and honored that both will be based at the University of Chicago,” said Glenn Steele, Dean of the Division of the Biological Sciences and Vice President for Medical Affairs at the University. “This builds on our remarkable history of advances in transplantation, immunology and diabetes research and recognizes the ongoing leadership of our many superb scientists, such as the research teams pulled together by Professor Bluestone.”

The JDF Center for Islet Transplantation

In patients with type 1, or juvenile, diabetes, the insulin-producing beta cells, found in pancreatic islets, have been destroyed. Scientists have been tantalized for more than 25 years by the idea of transplanting healthy islets but frustrated by the difficulty of protecting those islets from the recipient’s immune system, which rejects foreign tissue. Current techniques of protecting those islets suppress the entire immune system, increasing the recipient’s risk of infection and cancer.

“It’s like tearing down your house just to get rid of the mice,” said Bluestone. The JDF Center will try to improve islet transplantation through three major projects. Bluestone’s laboratory will concentrate on developing new, more specific therapies to induce immune tolerance by eliminating the components that attack the transplanted cells without impairing the rest of the immune system.

A team led by Bernard Hering, co-director of the JDF Center and an islet-transplant specialist at the University of Minnesota, will coordinate testing of these new therapies in human clinical trials.

A third team led by Kenneth Polonsky, Professor in Medicine, Section Chief of Endocrinology at the University and co-director of the JDF Center, will closely monitor all patients and their transplanted islets and assess the genetic and immunologic signals that result from these new therapies. These efforts to uncover exactly what triggers rejection could serve as a guide to develop even more effective therapies.

“Every one of us who has diabetes, or who has children with diabetes, knows that insulin is not a cure,” said JDF Chairman of the Board John J. McDonough. “This new JDF Center moves us closer to the day when we will be free from daily injections, constant concern about blood sugar levels and the dangers of blindness and the other debilitating health effects of type 1 diabetes.”

The Collaborative Network for Clinical Research on Immune Tolerance

Immune-mediated diseases, such as type 1 diabetes or arthritis, are very common, affecting tens of millions of Americans, including more than 19,000 organ-transplant recipients each year. These disorders result in direct and indirect annual costs of more than $100 billion in the United States alone. Successful and lasting induction of immune tolerance could potentially eradicate autoimmune disease and eliminate the need for permanent immune suppression in transplant patients.

The Collaborative Network––which will include more than 70 of the world’s leading immunology researchers and clinical specialists in transplantation and autoimmune disease from nearly 40 institutions in nine countries––will coordinate human clinical testing of new therapies designed to bring about immune tolerance.

“This collaboration brings together some of the brightest minds in immunology and flows from NIAID’s plan to accelerate clinical trials for novel approaches to modulate immune responses,” said NIAID Director Anthony Fauci. “Immune tolerance research has great potential to help millions afflicted with some of the most debilitating and chronic immune-mediated diseases.”

The goal is to learn how to persuade the immune system to accept certain beneficial tissues yet remain vigilant against harmful invaders. The network initially will focus on the challenges presented by the rejection of foreign tissues, such as transplanted kidneys or insulin-producing beta cells, and on the autoimmune diseases such as type I diabetes, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Eventually, it will expand to include clinical studies of immunologic treatments of asthma and allergic diseases.

Recent tests of new methods to induce immune tolerance have shown promising results in both animal models and early human clinical studies. Network researchers will accelerate testing of these and other tolerogenic approaches and will develop and evaluate methods to monitor the induction, maintenance and loss of immune tolerance in humans.

“We have established a collaboration that will be open and inclusive with the flexibility to capitalize on emerging opportunities for any tolerogenic approaches,” said Bluestone, a recognized pioneer in developing tolerogenic therapy.

The NIAID will supply more than $128 million for the network, with another $14 million provided by the JDF and additional support from the National Institute of Diabetes and Digestive and Kidney Diseases.