The standard treatment for type 1 diabetes¿an autoimmune disease in which healthy, insulin-secreting cells of the pancreas are destroyed?manages the complications of the disease. Diabetics monitor their blood sugar levels and inject themselves when necessary with insulin, the hormone responsible for breaking glucose down into fuel. But now researchers at Massachusetts General Hospital have actually retrained the malfunctioning immune cells of diabetic mice to behave properly. Their results appear in the July 1 issue of the Journal of Clinical Investigation.
The scientists studied immune cells of both diabetic mice and people for five years looking for clues that helped determine the two-step approach described in the study. After noticing that exposure to the naturally occurring compound TNF-alpha (Tumor Necrosis Factor-alpha) killed malfunctioning immune cells, the researchers stimulated expression of TNF-alpha in the mice. This approach is contrary to past interventions for type 1 diabetes¿often, doctors prescribe drugs to block TNF-alpha receptor sites.
The second step of the therapy addressed the immune cells?inability to present self-peptides, molecules that are required to halt the development of autoimmune diseases. The scientists injected the diabetic mice in their study with donor cells able to express the self-peptides in order to "teach" the newly emerging immune cells not to attack the insulin-secreting islet cells. Nearly 75 percent of the treated mice still had normal glucose levels more than 100 days after the treatment was stopped.
"With only a brief treatment, we have reversed an established autoimmune disease in a respected animal model," says Denise Faustman of the Immunobiology Laboratory at Massachusetts General Hospital and the lead author of the study. "Although the results are preliminary, this is an exciting finding for diabetes."