Can an 80-year-old TB vaccine cure diabetes?

Maybe. A small clinical study found "proof of principle" that the BCG tuberculosis vaccine might help adults with long-standing type 1 diabetes.

Over a decade ago, Denise Faustman, MD, PhD, and colleagues at Massachusetts General Hospital and Harvard Medical School showed that the BCG vaccine worked in diabetic mice. By stimulating positive immune responses, the vaccine stopped the haywire immune responses that cause diabetes. Once this happened, the animals' insulin-making cells regenerated.

Other researchers duplicated the mouse studies. This led to "a lot of happy mice," Faustman says. But translating the findings to humans hasn't been easy. For starters, it required learning a lot more about the immune system and a lot more about type 1 diabetes.

It didn't look promising. A 1999 study found no effect of BCG vaccination in kids newly diagnosed with type 1 diabetes.

"When we started, there wasn't too much enthusiasm about trying to reverse diabetes in people 15 to 20 years out with this disease," Faustman tells WebMD.

She persisted.

"Surprisingly, our data was so good we got a signoff on doing a safety trial from the FDA," she says. "Even more surprising was that in this safety study, at a very low dose and after only two BCG vaccinations, we started seeing indications that this vaccine is doing the same thing in people as it does in the mouse."

Slideshow: A Visual Guide to Type 1 Diabetes
Hopeful Signs but No Lasting Effect

In the study, six insulin-dependent adults with type 1 diabetes received either two doses of BCG or two fake vaccinations. The two groups were compared to one another, to 57 diabetes patients, and to 16 people without diabetes.

In the three patients who received the vaccine:

    "Bad" anti-insulin T cells began dying off.
    New "good" regulatory T cells increased.
    There were signs of new, albeit temporary, insulin production from pancreatic beta cells.
    The vaccine was safe.

The same things happened in one of the patients who received a placebo. This, Faustman says, is because the patient happened to come down with mononucleosis, a viral infection that triggered the same immune responses as the BCG vaccine.

"We did not kill all the bad T cells, but we killed a lot, and we also saw transient resurrection of C peptide [a sign of improved beta cell function]," Faustman says. "So now we will try to move forward with a phase-two study to figure out the right dose and the right frequency for benefit."

If the treatment works, patients likely would have to receive repeated BCG vaccinations -- probably for life. But Faustman says the vaccine's long history shows this would be safe.
Can BCG Work Where Other Immune Therapies Failed?

A lot more evidence will be needed before Faustman convinces most diabetes experts that she's on the right track. One skeptic is Steven Wittlin, MD, professor of medicine and director of the diabetes service at the University of Rochester, N.Y.

"We are always hoping for an immune cure for diabetes," Wittlin tells WebMD. "But so far all the immune studies that looked promising in early human studies have failed in large-scale trials."

Wittlin notes that previous efforts to treat or prevent type 1 diabetes with BCG vaccine have failed.

"But the devil may be in the details" of how Faustman's team is using the vaccine, he suggests.

Faustman hopes so, too. If this approach works in people with diabetes, she says, it may also work for people with other autoimmune diseases. Such diseases include Crohn's disease, lupus, scleroderma, rheumatoid arthritis, Sjogren's syndrome, and multiple sclerosis.

Faustman and colleagues are recruiting type 1 diabetes patients for a phase II clinical trial of the BCG vaccine; the study will not start until funding becomes available. So far, she's raised $11 million of the estimated $25.2 million cost.

The Faustman study appears in the Aug. 8 online issue of PLoS One.