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April 15, 2002

Diabetes center to address transplant rejection

By Holly Korschun


The need to make islet replacement successful as a viable cure for patients with juvenile diabetes (also known as Type 1 diabetes) received a boost last month with the launch of a new Juvenile Diabetes Research Foundation (JDRF) Center for Islet Transplantation at Emory.

The center is being funded with a three-year, $4.1 million grant and will address an important issue facing islet transplantation: rejection of donor islets by the patient’s immune system. Although islet transplantation from donor pancreases can restore normal insulin production in patients with Type 1 diabetes, several problems exist with current immunosuppressive protocols. The Emory center will ambitiously explore various initiatives toward the goal of insulin independence for these patients, without long-term immunosuppression.

Researchers will explore various interrelated approaches to reduce the requirements for immunosuppressive drugs. They also are investigating the use of less toxic drugs than current therapies and testing whether donor islets transplanted from animals can be protected in a delicate membrane from the body’s immune response.

Collin Weber, director of the new JDRF center, has had a distinguished career that includes 30 years of investigations in the field of diabetes research. Weber’s co-director is Christian Larsen, who will lead the clinical islet transplantation program. Larsen, director of the Emory Transplant Center, is recognized internationally for his work in devising strategies to achieve transplantation tolerance.

“Significant progress in islet transplantation was made in the Edmonton Protocol in Alberta, Canada, in patients with very severe, life-threatening problems with glucose control,” Weber said. “However we realize that wide-scale application of islet transplantation using conventional immunosuppressants is not feasible because of long-term side effects. Our goal here is ambitious and exciting and, if successful, will improve the effectiveness of transplants and create a larger source of donated islets.”

Two of the center’s projects will focus on using a steroid-free approach with a new class of compounds called “co-stimulation blockers.” One of these compounds has already shown promise to protect kidney transplants from attack by the immune system. In one project, investigators will carry out a clinical trial of human islet transplantation using the most promising drug. In the second related project, researchers will perform preclinical studies and examine “tolerance induction” to islet grafts using the co-stimulation blockade approach in nonhuman primates.

Other projects will focus on the use of microencapsulated pig islets to address the problem of limited availability of human pancreatic tissue. In these studies, investigators will examine the ability of pig islets encapsulated in a protective membrane to correct diabetes in laboratory mice. The researchers will work to optimize the design of the protective membrane to prevent immune attack of the pig islets while maintaining islet function. The technique may also be applied to the transplantation of human islets.

The Emory Transplant Center is one of the most comprehensive transplant centers in the South-east, featuring programs in heart, lung, liver, kidney and kidney-pancreas transplants and fostering cutting-edge basic, translational and clinical research to improve the effectiveness of transplantation.

JDRF is the world’s leading nonprofit, nongovernmental funder of diabetes research. Since its inception in 1970, JDRF has provided more than $500 million to diabetes research worldwide.

“The launch of this new center at Emory underscores JDRF’s determination to keep research on a fast track to find a cure for a disease affects more than 16 million Americans,” said Charles Queenan, chair of research for JDRF. “JDRF has been in the forefront worldwide with islet transplantation as one of its priorities. The possibilities are both tantalizing and frustrating, but the research must now focus on conquering autoimmunity and tolerance issues.”