June 29, 2001

Researchers at the MGH have shown that an unexpectedly simple treatment cures type 1 diabetes in mice. Published in the July 1 issue of the Journal of Clinical Investigation, the findings are distinct from the current theories about how to treat the disease.

"With only a brief treatment, we have reversed an established autoimmune disease in a respected animal model," says Denise Faustman, MD, PhD, of the MGH Immunobiology Laboratory and principal investigator of the study. "Although the results are preliminary, this is an exciting finding for patients with diabetes."

Normally, the body's immune cells attack toxins and foreign invaders, such as bacteria and viruses. In type 1 diabetes, however, the immune cells somehow receive a faulty signal, and their destructive efforts are instead directed toward the islet cells, the insulin-secreting cells of the pancreas. This results in a decrease of insulin — a molecule necessary for the conversion of glucose into fuel — and a subsequent increase in glucose. As glucose accumulates in the blood, it can damage organs, leading to conditions such as heart disease, kidney failure and blindness.

Faustman's treatment involves re-training the immune system of diabetic mice so that their islet cells are no longer under attack. Faustman and her team came across two key findings in diabetic mice and humans: the immune cells died when they were exposed to the naturally occurring drug, TNF-alpha, and many of the immune cells were unable to display self-produced peptides — a process crucial for preventing the development of autoimmune reactions.

Because of these findings, the team designed a two-pronged treatment strategy. First, they triggered the expression of TNF-alpha in the mice in an attempt to destroy the immune cells that had gone awry. This approach never had been used for the treatment of type 1 diabetes.

In the next step of the two-pronged approach, the researchers addressed the lack of self-produced peptide display. The diabetic mice were injected with donor cells that expressed the self-peptides, which re-trained the newly emerging immune cells of the mouse, ensuring that they did not attack the islet cells.

Up to 75 percent of the treated mice had normal blood glucose levels that persisted for more than 100 days after the treatment was discontinued. Faustman and her group found no need to administer islet cell transplants or to intervene before symptoms arise, the two major treatment approaches used for type 1 diabetic patients today. For more information about this study, visit the MGH home page at www.mgh.harvard.edu or www2.massgeneral.org.