10/08/2012
TB Vaccine Promising as New Way to Fight Type 1 Diabetes
A small trial of a vaccine already approved for tuberculosis found that the vaccine can kill the rogue autoimmune cells that are active players in type 1 diabetes.
There were no changes, however, in the need for insulin among those with longstanding diabetes who got the vaccine, the researchers added.
"What we saw with two vaccines, given four weeks apart, was the death of bad T-cells," said study author Dr. Denise Faustman, director of the immunobiology laboratory at Massachusetts General Hospital in Boston. "We also saw that regulatory T-cells came on -- these are the good-guy T-cells. And the pancreas went on briefly, and this was in people who were 15 years out from their type 1 diagnosis."
"This doesn't mean that people were throwing their insulin syringes away," Faustman said. "But the exciting part is that even decades after the disease begins, the cells in the pancreas can kick in again."
Results of the study appear online Aug. 8 in the journal PLOS One.
The vaccine, which has been approved by the U.S. Food and Drug Administration, is called bacille Calmette-Guerin (BCG), and has been used against tuberculosis for about 90 years, Faustman said. BCG also is used as a treatment for bladder cancer.
The vaccine works by increasing levels of a substance known as tumor necrosis factor (TNF). High doses of TNF can be toxic, but the vaccine doesn't appear to raise levels of TNF too high.
According to the U.S. Centers for Disease Control and Prevention, the only groups that shouldn't receive the live vaccine are those whose immune systems are compromised, such as people who have HIV or people who have received an organ transplant. The CDC also recommends against giving the vaccine to pregnant women because it hasn't been well-studied in this population.
In 2001, Faustman's team tested a similar substance in mice and found that it destroyed the harmful T-cells and allowed the insulin-producing cells in the pancreas to regenerate and produce insulin.
The question was: Would such regeneration take place in humans with type 1 diabetes if the immune-system attack that causes type 1 diabetes in the first place was stopped?
To answer that question, Faustman and her colleagues recruited six people with type 1 diabetes who were randomly assigned to receive two injections of either the vaccine or a placebo, and they were compared to one control group without diabetes and one with the disease.
The average duration of type 1 diabetes at the beginning of the study was 15.3 years, and the average age of those with diabetes was 35.
During the 20-week study, two out of the three people treated with BCG had evidence of bad T-cell death and increases in the levels of protective T-cells. They also showed an elevation in levels of a substance called C-peptide that indicates insulin production.
Faustman said it's not clear why BCG didn't appear to help one of those treated with it, but, she added, at the end of the study, the individual's level of C-peptide began to increase.
She also said it's not yet certain whether more frequent doses or higher doses would be needed to restore more pancreatic function, but it may matter how long someone has had the disease.
Faustman said, however, that no matter how long someone has had the disease, they'll likely get some function back.
"We may only restore 5, 10, 20, 50 or 60 percent of function -- we just don't know yet -- but any restoration of C-peptide helps to prevent diabetes complications," she said.
One expert said the finding was important, but many questions remain.
"This study shows that by increasing TNF, they can induce the death of the autoreactive T-cells that destroy the cells that make insulin, and they transiently increase C-peptide levels," said Dr. Spyros Mezitis, an endocrinologist at Lenox Hill Hospital in New York City. "But what happens after 20 weeks? How often would they need to give this vaccine?"
"I'm concerned about increasing the levels of TNF in the body," he added. "They're saying that only the insulin-secreting cells are affected, but what are the long-term effects if it's given repeatedly? What about the growing cells in children, because if it works it would be used in children."
Still, he said, "this is important research that helps us understand the pathophysiology of type 1 diabetes."
Faustman said that BCG has an excellent safety record, and has been given to billions of adults and children worldwide to prevent tuberculosis.
Faustman and her colleagues are currently developing phase II trials to test using higher levels of the vaccine
