Andrew H's answer is only somewhat correct, the 3 patients were only the first phase of the first phase (ha), the grand total seems to be 9; still this treatment is controversial, something that was hinted well enough in the source used for the question (at the end of the article, several experts cautioned about the small sample size). Another article employes thinner gloves... on both sides of the issue:
While the results, from only nine patients, must be replicated in a larger study, said Dr. Joseph Bellanti of Georgetown University Medical Center, “if what they found is true, they really have something here.” Bellanti, who was not involved in the research, said the study’s eight-year follow-up and use of a placebo control arm made him “cautiously optimistic” that two doses of the BCG vaccine “can decrease levels of A1c,” a measure of blood glucose that predicts the likelihood of serious complications such as stroke and kidney failure.
JDRF (formerly the Juvenile Diabetes Research Foundation), the Joslin Diabetes Center, and several university diabetes centers all declined to speak about Faustman’s results. She has been a voice in the diabetes wilderness for nearly two decades, angering the establishment diabetes community by pursuing low-tech research very different from more popular approaches, such as embryonic stem cells and immunosupression.
Critics have gone so far as to send letters to newspapers that covered her work apologizing to patients “on behalf of Dr. Faustman” for “having their expectations cruelly raised.” She has also struggled for funding, receiving much of her research support from the private Iacocca Family Foundation, rather than in federal grants.
In Faustman’s Phase 1 clinical trial, three participants with type 1 diabetes received two doses of BCG vaccine, a month apart. After the vaccine showed signs of effectiveness, an additional six patients were vaccinated five years ago, and 111 more recently. The new paper and a presentation scheduled for a meeting of the American Diabetes Association this weekend focus on the patients who have been followed for more than five years.
“We wanted it to be good, but we didn’t know it would be this good,” Faustman said.
All of the patients remain on insulin, she said, but less of it. They are also able to monitor their blood sugar less frequently, which can be several times an hour. (The standard of care is a continuous glucose monitor, in which a probe is inserted into the abdomen, plus an insulin pump.) “If we can gradually move people to where they can control their blood sugar, their minute-to-minute lifestyle can improve dramatically,” Faustman said.
The A1c reductions could also bring significant health benefits. Every 10 percent drop, research shows, reduces complications such as stroke and heart attack by about one-third. The BCG vaccine lowered A1c levels 9 percent to 16 percent.
A Phase 2 clinical trial of BCG is currently underway at Mass. General. It is testing multiple BCG doses in 150 patients with longstanding type 1 diabetes.
Although many studies of BCG are underway around the world in diabetes and other autoimmune diseases, including multiple sclerosis, there has been little interest among U.S. researchers outside Faustman’s lab.
“There is not a lot of enthusiasm because we’re all rewarded for discovering for-profit drugs,” she said. “Potential funders come [to my lab] and ask, ‘How can we make money off this?’”
BCG, whose one licensed manufacturer in the U.S. is Merck subsidiary Organon Teknika, costs less than a dollar a dose. (Faustman used a strain made by Sanofi.) The U.S. market for insulin meters and insulin pumps is $20 billion. “With everyone thinking they need a pump and a meter, if you come along with an inexpensive vaccine that can change this standard of care, of course there will be pushback,” Faustman said.
So I doubt this will have a satisfactory answer until the larger (150 patient trial) concludes.
Also, Reuters reported some putative mechanisms of action being investigated and perhaps even replicated (by others) in mice, so Andrew's part of the answer on that seems incorrect. I'm not in a position to evaluate the plausibility of the mechanism myself, and certainly some other researchers appear to have dissed it:
The study is nevertheless within the mainstream of current efforts to cure diabetes, said cellular immunologist Raphael Clynes of the Berrie Center, who was not involved in the research.
"Folks had presumed that by the time patients had overt diabetes, all their islet cells had been destroyed," Clynes said. "We now know there are preserved islet cells many years out. The presumption is, if you can get rid of the inflammatory, autoimmune response, the islet cells could regenerate."
Faustman's research on lab mice, begun in the 1990s, suggested that one way to get them to do that was with a compound in the body called tumor necrosis factor. TNF is difficult to obtain commercially, but the BCG vaccine increases the body's production of it.
Raising levels of TNF through the vaccine cured type 1 diabetes in mice, Faustman reported a decade ago: With the autoimmune T cells out of the picture, islet cells regenerated and began producing healthy amounts of insulin. The journal that published the study insisted Faustman not use the word "regeneration," so controversial was the idea that islets could come back to life. She substituted "restoration."
By 2006, other scientists - including some who had attacked Faustman's claims of regeneration - had replicated key findings of her mouse studies, laying the foundation for the clinical trial.
Three patients with longstanding diabetes received two injections, four weeks apart, of BCG. Three others received saline injections, serving as the placebo control.
In two of the three BCG patients, levels of islet-attacking T cells fell, the scientists reported on Wednesday. Dead autoimmune cells were released into the bloodstream, a hint that TNF was killing them as intended. A measure of insulin production rose. The only placebo patient with similar results had become infected with the Epstein-Barr virus, which also triggers production of TNF.
Althoug in other respects, the Reuters coverage reiterates the criticism with a bit more detail:
Faustman has already faced significant challenges to her theory. JDRF rejected her funding requests and circulated a 2003 letter from two of her colleagues at Harvard Medical School, casting doubt on her work and apologizing to diabetics for "having their expectations cruelly raised" by stories about her research.
Reaction to this study was not much better. "The paper shows that BCG is associated with a transient improvement in a couple of patients, but it's hard to conclude that TNF is the causative factor," said Columbia's Clynes.
"It's certainly interesting and worth further investigation," said JDRF Chief Executive Jeffrey Brewer. "But it's really important to be careful about how we interpret early results." Curing type 1 diabetes may finally be within reach, he said, "but it will be a marathon, not a sprint.
