An experimental vaccine designed to tamp down the abnormal immune response that causes Type 1 diabetes helped preserve patients' insulin-producing cells in a study that may change the way the disease is treated.
Researchers from Stanford University in California and Leiden University Medical Center in the Netherlands created a vaccine that selectively targets the destructive immune cells and stops their attack. The data, from the second of three stages of tests generally needed for regulatory approval, were published Wednesday in the journal Science Translational Medicine.
Type 1 diabetes is caused when the body's immune system destroys insulin-releasing cells in the pancreas, called beta cells, requiring patients to inject themselves with insulin replacement therapy. Scientists have long sought a treatment approach that targets the cause of the disease.
"Although insulin saves people's lives and was discovered 100 years ago, we need something better than that," Lawrence Steinman, a professor at Stanford School of Medicine near Palo Alto, Calif., and an author of the study, said in a telephone interview. "One of the long sought-after goals of immunological therapy is to do just this, antigen-specific modulation."
Type 1 diabetes, also called juvenile diabetes, affects as many as 3 million people in the U.S., according to JDRF, an organization that funds research for the disease. It's less common than Type 2 diabetes, which develops when the body becomes resistant to insulin or the pancreas stops producing enough insulin, and is linked to excess weight.
The compound, called TOL-3021, boosted the function of pancreatic beta cells and specifically reduced the killer immune cells implicit in Type 1 diabetes.
The trial was done in 80 patients ages 18 to 40 who had been diagnosed with Type 1 diabetes within 5 years. Patients were given an injection of the compound or placebo once a week for 12 weeks, and researchers looked at levels of C-peptide as a marker of the function of insulin-producing beta cells.
Patients taking a 1-milligram dose of TOL-3021 had their C- peptide levels rise 20 percent, compared with a decline of 8.8 percent for patients on placebo, the researchers reported. Immune cells known as T cells that directly targeted the pancreatic beta cells were shown to decline in patients taking the drug, while other T cells weren't affected. The study turned up no serious side effects.
Steinman said a next step is to conduct a longer trial with more patients to determine how the drug works over a period as long as a year, and to pursue treatment of patients at different stages of the disease.
"We do want to look at treatment of children, and the ultimate would be to see if we can treat those at risk before they get the disease and do this in a preventive way," Steinman said. On the other end of the spectrum, "it could provide benefit, as we've seen here, to people who were diagnosed a few years ago as long as they have some islet cells to preserve."
Steinman and colleagues formed a company around the technology in April, called Tolerion Inc. They are looking at partnerships with pharmaceutical companies "and other vehicles for moving ahead," he said. The company may be able to use the platform in other autoimmune diseases in which the target of the errant immune response is known, such as Grave's disease, he said.
"The wind at our back is the good data we've seen in this trial," Steinman said.