Research ArticleDiabetes

Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes

Science Translational Medicine  26 Jun 2013:
Vol. 5, Issue 191, pp. 191ra82
DOI: 10.1126/scitranslmed.3006103

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Diabetes Trial Hits Its Mark

Type 1 diabetes is an autoimmune disease where an inflammatory response destroys the insulin-producing cells of the pancreas. One way to block this response is through immunosuppression; however, it has proven difficult to target the specific autoreactive cells without suppressing the rest of the immune response. Now, Roep et al. demonstrate that an engineered plasmid that expresses proinsulin can preserve β cell function in type 1 diabetes patients.

The authors randomized patients recently diagnosed with type 1 diabetes to receive various doses of either a proinsulin-expressing engineered plasmid or PBS vehicle. They observed no serious adverse events. The subjects in the experimental group had improved C-peptide levels—a readout of β cell function. The authors then examined the immune responses in these patients and found that there was a decrease in proinsulin-specific CD8+ T cells, but not unrelated CD8+ T cells. No difference was observed in cytokine production by CD4+ T cells. If these data hold true in larger studies, a plasmid encoding proinsulin could serve as a targeted means of immunosuppression for type 1 diabetes.