Featured Research

from universities, journals, and other organizations

Clinical trial results support strategy for reversing type 1 diabetes: Treatment with generic vaccine kills autoimmune cells, temporarily restoring insulin production

Date:
August 9, 2012
Source:
Massachusetts General Hospital
Summary:
A phase I clinical trial has confirmed that use of a generic vaccine to raise levels of an immune system modulator can cause the death of autoimmune cells targeting the insulin-secreting cells of the pancreas and temporarily restore insulin secretion in human patients with type 1 diabetes.

A phase I clinical trial has confirmed that use of a generic vaccine to raise levels of an immune system modulator can cause the death of autoimmune cells targeting the insulin-secreting cells of the pancreas and temporarily restore insulin secretion in human patients with type 1 diabetes. Results of the study -- led by Denise Faustman, MD, PhD, director of the Massachusetts General Hospital (MGH) Immunobiology Laboratory -- are being published in the open-access journal PLoS ONE, and a larger Phase II trial is currently underway.

Faustman's team first reported in 2001 that inducing expression of tumor necrosis factor (TNF), previously shown to destroy insulin-autoreactive T cells, cured type 1 diabetes in mice by permitting pancreatic islets to regenerate. Since high doses of TNF are toxic to humans, the clinical trials use the bacillus Calmette-Guιrin (BCG) vaccine, which safely elevates TNF levels. The Iacocca Family Foundation has been the primary supporter of this work.

"We believe we have validated in humans the treatment pathway we originally reported in mice and are seeing early evidence of effectiveness," says Faustman. "Our findings show that this simple, inexpensive vaccine modifies the autoimmunity underlying type 1 diabetes, boosting TNF production and killing the disease-causing T cells, which appears to briefly restore pancreatic beta-cell function. This is not a prevention trial. We are trying to create a regimen that will actually reverse type 1 diabetes in people who are living with the disease. We anticipate that the Phase II trial will give us more direction for turning BCG into a more sustained treatment, including the right dose and the frequency of vaccination needed to sustain a therapeutic response."

A generic drug with over 90 years of clinical use, BCG is currently approved by the Food and Drug Administration for vaccination against tuberculosis and for the treatment of bladder cancer. The double-blind Phase I trial enrolled six long-term type 1 diabetes patients -- diagnosed for an average of 15 years -- who were randomly assigned to receive two doses of either BCG or a placebo spaced four weeks apart. Blood samples from the participants with diabetes were also compared with samples from six nondiabetic control participants and with samples from 75 additional individuals with diabetes and 15 without. Frequent blood tests measured participants' blood levels of insulin-autoreactive T cells, of an autoantibody, of regulatory T cells that help control the immune response, and of C-peptide, a marker of pancreatic insulin secretion.

During the 20-week study period, two of the three participants treated with BCG showed increases in the death of insulin-autoreactive T cells and in levels of protective regulatory T cells. A temporary but statistically significant elevation in C-peptide levels, suggesting a restoration of insulin production, was also observed in the BCG-treated patients. Unexpectedly, the same responses were seen in one of the placebo-treated patients who, after enrolling in the study, coincidently developed infection with the Epstein-Barr virus, which is known to induce expression of TNF. There were no significant adverse events. The researchers expect that more frequent or higher BCG dosing than was used in this trial will be needed for long-term elimination of insulin-autoreactive T cells and a sustained restoration of C-peptide secretion and insulin production.

"This is an exciting time for type 1 diabetes research," says Paul Burn, PhD, chair and director emeritus of the Sanford Project and professor of Pediatrics at the Sanford School of Medicine at the University of South Dakota. "Dr. Faustman and her team's clinical research data indicate that modifying the autoimmunity underlying type 1 diabetes allows for a safe and temporary restoration of insulin-secreting beta-cell function in patients with established type 1 diabetes. Restoring beta-cell function is a promising first step towards a cure. During my tenure in industry, at Sanford Health and at the Juvenile Diabetes Research Foundation, I have seen how hard it is to get a project from mice into humans, and these are very impressive results."

These findings are consistent with recent trials in Italy that showed BCG vaccination could decrease disease activity and prevent progression of brain lesions in advanced multiple sclerosis, an autoimmune disease also caused by autoreactive T cells vulnerable to TNF-triggered cell death. A recent Turkish study suggested that repeat BCG administration, but not single a BCG vaccination, could prevent diabetes onset in children and that childhood BCG vaccinations prevent the formation of autoantibodies. The PLoS One paper reflects a 20-year journey for the Faustman lab from understanding the role of TNF to developing a way to measure death of the disease-causing T cells in type 1 diabetes and redefining how the pancreas functions in individuals who have had diabetes for decades.

In addition to providing major funding for the now-completed Phase I trial, the Iacocca Family Foundation has committed to a leadership role in the Phase II clinical trial. Currently, $11 million has been raised out of a total of $25 million needed to conduct the Phase II study over the next three years.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Denise L. Faustman, Limei Wang, Yoshiaki Okubo, Douglas Burger, Liqin Ban, Guotong Man, Hui Zheng, David Schoenfeld, Richard Pompei, Joseph Avruch, David M. Nathan. Proof-of-Concept, Randomized, Controlled Clinical Trial of Bacillus-Calmette-Guerin for Treatment of Long-Term Type 1 Diabetes. PLoS ONE, 2012; 7 (8): e41756 DOI: 10.1371/journal.pone.0041756

Cite This Page:

Massachusetts General Hospital. "Clinical trial results support strategy for reversing type 1 diabetes: Treatment with generic vaccine kills autoimmune cells, temporarily restoring insulin production." ScienceDaily. ScienceDaily, 9 August 2012. <www.sciencedaily.com/releases/2012/08/120809090538.htm>.
Massachusetts General Hospital. (2012, August 9). Clinical trial results support strategy for reversing type 1 diabetes: Treatment with generic vaccine kills autoimmune cells, temporarily restoring insulin production. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2012/08/120809090538.htm
Massachusetts General Hospital. "Clinical trial results support strategy for reversing type 1 diabetes: Treatment with generic vaccine kills autoimmune cells, temporarily restoring insulin production." ScienceDaily. www.sciencedaily.com/releases/2012/08/120809090538.htm (accessed April 24, 2014).

Share This



More Health & Medicine News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) — Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) — A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) — Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) — NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins