Blocking Autoantibody Formation Prevents Diabetes in Mouse Model

Mice that had been genetically engineered to develop spontaneously diabetes were protected from the disease by a low molecular compound, which prevented the formation of autoantibodies that would normally have attacked insulin-producing cells.

Investigators at the University of Colorado School of Medicine (Denver) worked with the NOD line of diabetes-prone mice. They injected a group of these animals with the compound glyphosine. Glyphosine is a drug candidate that was identified after screening more than 139,000 compounds for the ability to block autoantibody formation.

Glyphosine functioned by binding to a pocket in one of the histocompatibility molecules that are directly responsible for production of autoantibodies. By doing so, it enhanced insulin peptide presentation to T cells at concentrations as low as 10 nmol, upregulated IL-10 secretion, and prevented development of diabetes in the NOD mice. The drug had no effect on animals that were already diabetic. These findings were reported in the October 31, 2011, online edition of the Journal of Immunology.

“We found that when you put specific molecules into specific structural pockets you can block the formation of diabetes,” said senior author Dr. George Eisenbarth, professor of pediatrics, medicine, and immunology at the University of Colorado School of Medicine. “We are basically throwing a monkey wrench into the machinery.”

The investigators believe that it would be feasible to screen genetically individuals likely to develop diabetes and begin a therapy regimen using compounds like glyphosine to prevent the onset of the disease.

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