Sign up for our complimentary
weekly e-journal

Main Newsletter
Mastery Series
Therapy Series
 
Bookmark and Share | Print Article | Items for the Week Previous | All Articles This Week | Next
This article originally posted and appeared in  MedicationType 1 DiabetesPathologyIssue 640

Faustman's Type 1 Diabetes Cure Raises Debate

Dr. Denise Faustman's announcement of the results of a small study of a handful of type 1 patients showing the regeneration of beta cells with the use of a TB vaccine that has been available for years is causing a controversy in the medical community....

Advertisement

If the findings do hold up, however, they would mean that the generic TB vaccine, in use since 1921, can regenerate insulin-secreting cells in the pancreas.

But there is no guarantee the results from this early-stage trial, published on Wednesday in PLoS One, will stand up in larger studies, which are now under way. Other diabetes researchers criticized it for going beyond the evidence in its claims about what caused the observed effects.

Dr. Denise Faustman of Massachusetts General Hospital, who led the trial, stated that, "We think we're seeing early evidence of effectiveness." "This simple, inexpensive vaccine attacks the autoimmunity underlying type 1 diabetes."

"We found that even low doses of the vaccine could transiently reverse type 1 diabetes, and this was in patients who have had the disease for 15 years." The effect lasted for about one week. "Our measurements showed that autoimmune T cells that destroy the islet cells died, and we saw evidence that insulin production was restored."

Dr. Domenico Accili of the Naomi Berrie Diabetes Center at Columbia University Medical Center, who did not participate in the study, has doubts. "There is a bit of magical thinking in the concept." "The idea that BCG wipes out autoimmune cells is totally unproved."

Cellular immunologist Dr. Raphael Clynes of the Berrie Center, who was not involved in the research, stated that, "Folks had presumed that by the time patients had overt diabetes, all their islet cells had been destroyed." "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 regenerate was with tumor necrosis factor. TNF is difficult to obtain commercially, but the BCG vaccine increases the body's production of it.

Dr. Faustman reported a decade ago that, raising levels of TNF through the vaccine cured type 1 diabetes in mice. 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 Dr. Faustman not use the word "regeneration," so controversial was the idea that islets could come back to life. She substituted "restoration."

Three patients with longstanding diabetes received two injections of BCG, four weeks apart. Three others received saline injections.

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.

The scientists also reported marked increases in C-peptide levels, a marker of the body's own insulin production. (They did not measure insulin itself because insulin made by the pancreas cannot be distinguished from the injected form.) "It wasn't to the level where they could throw away their syringe, but it was a significant elevation," said Dr. Faustman. "And this was in patients 15 years out: Their islet cells weren't dead, as most people said."

The restored insulin production lasted only a week. In the trial for which Dr. Faustman is recruiting the first of hundreds of patients she therefore plans to give more frequent BCG shots.

This is not the first time that Dr. Faustman has faced significant challenges to her theory. The Juvenile Diabetes Research Foundation 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. It's worth noting that this is not the first time BCG (tuberculosis vaccine) has been studied – several previous trials have failed -- and several members of the diabetes research community were extremely skeptical about BCG in general, as well as this particular trial. (Faustman believes previous trials failed because of a lack of knowledge about mechanism and incorrect dosing.)

Columbia's Dr. Clynes stated that, "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."

"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."

Dr. Faustman's team says the study was funded "by philanthropic grants only."

PLoS Clinical Trials, 8-15-2912 

Advertisement


 

Bookmark and Share | Print | Category | Home

This article originally posted 23 August, 2012 and appeared in  MedicationType 1 DiabetesPathologyIssue 640

Past five issues: Issue 796 | Diabetes Clinical Mastery Series Issue 255 | Issue 795 | SGLT-2 Inhibitors Special Edition August 2015 | Diabetes Clinical Mastery Series Issue 254 |

2015 Most Popular Articles:

Coffee Consumption Proves Potential in Reducing Type 2 Diabetes Risk
Posted August 07, 2015
Impaired Glucose Uptake in the Brain May Increase Alzheimer's Disease Risk
Posted August 07, 2015
First Non-Surgical Weight Loss Procedure for Mild-to-Moderate Obesity
Posted August 07, 2015
Ketoacidosis Not as Great as Thought in Diabetes Patients Taking Invokana
Posted August 13, 2015
GLP-1 Agonist Semaglutide Completes Phase III Trial with Positive Results
Posted August 07, 2015
Impact of Switching Insulin Glargine to Insulin Detemir in T2 Patients
Posted August 14, 2015
SIgnificant Weight Gain Associated with Laparoscopic Sleeve Gastrectomy
Posted August 14, 2015
Two New Possible Methods for Diagnosing and Monitoring Diabetes
Posted August 07, 2015
Diabetes Combination Drug LixiLan Meets Main Target in Late Stage Trial
Posted August 07, 2015
Soybean Oil Causes More Obesity and Diabetes Than Fructose
Posted August 20, 2015


Browse by Feature Writer & Article Category.
A. Lee Dellon, MD | Aaron I. Vinik, MD, PhD, FCP, MACP | Beverly Price | Charles W Martin, DD | Derek Lowe, PhD | Dr. Brian Jakes, Jr. | Dr. Fred Pescatore | Dr. Tom Burke, Ph.D | Eric S. Freedland | Evan D. Rosen | Ginger Kanzer-Lewis | Greg Milliger | Kristina Sandstedt | Laura Plunkett | Leonard Lipson, M.A. | Louis H. Philipson | Maria Emanuel Ryan, DDS, PhD | Marilyn Porter, RD, CDE | Melissa Diane Smith | Michael R. Cohen, RPh, MS, ScD, FASHP | Paul Chous, M.A., OD | Philip A. Wood PhD | R. Keith Campbell, Professor, B.Pharm, MBA, CDE | Richard K. Bernstein, MD | Sheri R. Colberg PhD | Sherri Shafer | Stanley Schwartz, MD, FACP, FACE | Steve Pohlit | Steven V. Edelman, M.D. | Timothy S. Hollingshead |

Cast Your Vote
What percentage of your patients have reached goal for A1c, BP and cholesterol?

CME/CE of the Week
William Tamborlane, MD, FAAP, FACE

Category: General Diabetes
Credits:
 .75