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Generic bacillus Calmette-Guérin (BCG) vaccine shows potential in reversing advanced type 1 diabetes by restoring proper immune response to pancreatic islet cells, according to findings presented at the 75th Scientific Sessions of the American Diabetes Association.

BCG is derived from a harmless bacterial strain that causes tuberculosis and has been around for more than a century. It currently has U.S. Food and Drug Administration approval for TB and bladder cancer treatment. However, a number of studies worldwide have been testing its potential as an agent for preventing and reversing autoimmune diseases like type 1 diabetes.

According to Denise Faustman, MD, PhD, director of the Massachusetts General Hospital Immunobiology Laboratory and principal investigator of the trial, BCG is of interest due its ability to permanently restore beneficial Treg genes through repeat vaccinations—thus halting the abnormal self-reactivity in type 1 diabetes. This process of modulating gene expression is known as epigenetics and could apply to other autoimmune diseases, Faustman said in a statement. Such a discovery “now provides a better idea of how BCG vaccination appears to work by powerfully modulating Treg induction and resetting the immune system to halt the underlying cause of the disease,” she said.

Faustman’s team trailblazed this effort first by recording type 1 diabetes reversal in mice, then advancing to a successful phase I clinical trial in humans with long-term diabetes. The phase 1 clinical trial with results reported in 2012 found that “two injections of BCG spaced four weeks apart led to temporary elimination of diabetes-causing T cells and provided evidence of a small, transient return of insulin secretion,” according to a statement from Massachusetts General Hospital.

Investigators in a phase II trial plan to vaccinate test subjects on a more frequent basis over a 4-year period, to examine the longer-term effects of this approach. The trial will include a BCG vaccination cohort and a placebo cohort. The thinking is the disease will progressively diminish with each vaccination, enabling white blood cells to strengthen the pancreas and restore insulin secretion.

Faustman observed, “The vaccine’s beneficial effect on host immune response recapitulates decades of human co-evolution with myocbacteria, a relationship that has been lost with modern eating and living habits. It is incredible that a safe and inexpensive vaccine may be the key to stopping these terrible diseases.”