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Two antibody injections reverses type 1 diabetes in mice

Kathleen Blanchard's picture
Researchers from UNC reverse type 1 diabetes in mice with immunotherapy.

Researchers have been trying to find a way to reverse type 1 diabetes using immunotherapy that boosts antibodies in the body. Scientists at the University of North Carolina School of Medicine have shown for the first time that injections of ‘non-depleting’ antibodies might someday reverse the disease for people recently diagnosed with the disease.

‘Non-depleting’ antibodies successful for reversing diabetes

Immunotherapy that blocks type 1 diabetes has been largely unsuccessful because antibodies to halt destruction of beta-cells in the pancreas also deplete specialized cells in the body that are important for fighting disease, known as T-cells. The researchers for the current study found they could use so-called non-depleting antibodies to reverse type 1 diabetes in non-obese diabetic mice without destroying disease fighting T-cells.

Senior study author Roland Tisch, PhD, professor of microbiology and immunology at UNC explains type 1 diabetes leads to destruction of insulin producing beta cells in the pancreas because of attack from ‘autoreactive’ T-cells, which are also important for destroying bacteria and viruses.

"Clinically, there have been some promising results using so-called depleting antibodies in recently diagnosed Type 1 diabetic patients, but the disease process is blocked for only a short period of time," Tisch said in a press release. "These antibodies don't discriminate between T cells normally required for maintaining immunity to disease-causing pathogens and the autoreactive T cells.”

He says depleting antibodies used for immunotherapy only transiently reverses the disease and also comes with complications.

The scientists decided to explore non-depleting antibodies that bind selectively to CD4 and CD8 proteins expressed by all T cells.

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When they gave non-obese diabetic mice that are a human model for type 1 diabetes the non-depleting antibodies, blood sugar levels normalized within 48 hours and within 5 days 80% of the mice experienced reversal of the disease.

The mice received just 2 antibody treatments and after more than 400 days most of them remained free from type 1 diabetes.

Even though the antibodies were cleared after 2 to 3 weeks the mice were still protected. "The protective effect is very rapid, and once established, is long-term," Tisch said.

Beta-cell destruction was halted from just 2 immunotherapy treatments. The researchers found all of the T-cells that destroy insulin producing beta-cells had been purged from the pancreas, but the number of T-cells in other tissues remained unaffected. "

Tisch says, “We've demonstrated that the use of non-depleting antibodies is very robust. We're now generating and plan to test antibodies that are specific for the human version of the CD4 and CD8 molecules."

Another finding was that the immunotherapy using ‘non-depleting’ antibodies boosted the number of T-cells that protect from autoimmune diseases like type 1 diabetes. The new study is promising because it shows type 1 diabetes might be quickly reversed with antibody immunotherapy that targets specific proteins in T-cells, thus preserving overall immune function.

UNC Health Care
July 5, 2012

Image credit: Morguefie