Antibody Prevents Type 1 Diabetes

University of Pittsburgh investigators have successfully prevented the onset of type 1 diabetes This study was funded by the NIH ACE (Autoimmunity Center of Excellence) at the University of Pittsburgh, Pennsylvania, and led by Dr. William M. Ridgway.

The investigators treated NOD mice with anti-CD137 antibody, which caused the production of CD4 and CD25 cells.
NOD mice treated with anti-CD137 antibodies were not protected from insulinitis, and they still harbored pathogenic T cells. However, transfer of CD4 and CD25 cells from treated mice to untreated NOD mice prevented the development of diabetes.
Dr. Ridgway explained, "The treatment did not eliminate the autoreactive T cells." "This is what led us to discover that the mechanism of action of the antibody was to boost the T regulatory cells, which ‘blocked’ the autoreactive T cells from destroying the islets, even though there was still insulitis."

"So, it is possible that the protective effect on the T regulatory cells, could eventually ‘wear off,’ resulting in disease," The University of Pittsburgh researcher noted. "This suggests you might have to re-treat at some point to preserve the protective effect."

"We think this (antibody treatment) would most safely be used to boost T regulatory function prior to disease onset– that is, in the pre-diabetic phase as a preventive measure. This implies that the ongoing effort to genotype patients at risk for type 1 diabetes would have to proceed in order to, 1), identify patients at high genetic risk for diabetes and, 2), identify whether CD137 is playing a role in human diabetes."

Dr. Ridgway said that anti-CD137 antibody treatment could have adverse effects. It "could theoretically stimulate activated effector T cells with the result of enhanced autoimmunity. This is why its role is likely proscribed to an early disease state. Although we have not actually seen enhanced autoimmunity in older mice treated with the antibody, it is a theoretical concern."
Diabetes 2007;56:186-196.

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