Protein fragment halts type I diabetes

A protein-based drug injected into people who are just starting to show signs of diabetes can stop the disease in its tracks, two studies show. The research trials offer hope that early intervention can prevent or curtail type I, or juvenile-onset, diabetes.

In type I diabetes, the immune system destroys insulin-producing beta cells housed in the pancreas. This damage leaves a person unable to process sugars.

Immunologist Dana Elias, while at the Weizmann Institute of Science in Rehovot, Israel, in the 1990s, made a surprising discovery. She found that the immune system in one strain of diabetic mice produced antibodies to their own heat-shock protein 60.

Apparently, immune sentinels called T cells had misidentified the heat-shock protein 60 as foreign, and in the process, unleashed inflammatory proteins that incited an autoimmune attack on beta cells. Normally, heat-shock proteins protect other proteins inside a cell from being damaged by extreme heat or other stress.

Elias and her colleagues also found that giving extra copies of a heat-shock protein 60 fragment called p277 to mice with diabetes symptoms spares beta cells from the immune onslaught. The treatment works by inducing T cells to curb production of inflammatory proteins.

In the Nov. 24 Lancet, the researchers report that this therapy works in people. They gave three injections of p277 over 6 months to 16 people who had early signs of type I diabetes; 15 similar patients received inert injections. After 7 months, blood tests showed that volunteers getting these placebo injections were making only one-third as much

C-peptide–a marker of insulin production–as they had at the start of the study. After 10 months, that had fallen to one-fourth.

In contrast, people getting p277 maintained production of C-peptide. Not surprisingly, patients receiving p277 required less insulin to process sugar from food than those getting the placebo did, says Elias, who is now at Rehovot-based Peptor, a company that manufactures p277. Patients will probably need four to six injections of p277 per year, she says

In a second study, immunologist Bart O. Roep of Leiden University Medical Center in the Netherlands and his colleagues report similar results after giving 48 newly diagnosed diabetes patients in Belgium shots of p277 or a placebo. Roep’s team also found that p277 induces T cells to make fewer inflammatory proteins and hence preserves beta cells. Roep presented his findings in September at the 37th Annual Meeting of the European Association for the Study of Diabetes in Glasgow, Scotland. The study by Elias and her colleagues “is consistent with what we’re seeing,” Roep says.

Beta-cell destruction can take years. The traits that make these cells susceptible to attack in diabetes patients, and even the identities of the killers, are still being worked out, says Jerry P. Palmer, a physician at the University of Washington in Seattle. Nevertheless, he finds it exciting that a protein such as p277 can switch T cells away from making inflammatory proteins.

The vast majority of diabetes patients worldwide have type II diabetes, which is largely caused by cells’ failure to use the body’s insulin. Some of these patients, however, probably have autoimmune beta-cell destruction, Elias says, making p277 a possible treatment for them, too.