Protease treatment delays diabetes onset in diabetes-prone nonobese diabetic (NOD) mice

It has recently been demonstrated that proteolytic enzyme treatment modulates certain immune-mediated diseases. We have, therefore, studied the effect of administration of a protease mixture in the NOD mouse, an elegant animal model for autoimmune insulin-dependent diabetes mellitus (IDDM). Female NOD mice were fed proteolytic enzymes from age 6 weeks to 10 weeks, within the subclinical phase of IDDM. Once a week animals received intragastrically 1 mg Phlogenzym(R) (n=10 mice) or 0.5 mg Phlogenzym(R) (n=10) in 0.5 ml saline or saline only (n=10). Mice were followed for development of IDDM up to week 23. At week 21, all control animals were diabetic, whereas 25% of the treated mice were still normoglycemic al the end of the observation period. No significant appearance of autoantibodies against either isoform of the important islet cell antigen glutamic acid decarboxylase (GAD), GAD65 and GAD67, was observed in the mouse sera as determined by a highly sensitive radioimmunoassay. The histopathological examination of pancreatic islets showed signs of insulitis in ail mice with a tendency of milder insulitis in the protease-treated groups.