Reversing Type 1 Diabetes May Be Possible With Tuberculosis Vaccine
BCG therapy may enhance immune response in patients with T1D.
According to data from a recent phase 1 trial directed by the Massachusetts General Hospital Immunobiology Laboratory, the vaccine bacillus Calmette-Guérin (BCG) may have the potential to reverse type 1 diabetes. This interim report was presented at the American Diabetes Association 77th Scientific Sessions, held June 9-13 in San Diego, CA, by Denise Faustman, MD, PhD and her team — the first to document the reversal in mice.
Type 1 diabetes is an autoimmune disease presenting as an overall loss of pancreatic islets which are responsible for the endocrine activity of the pancreas. Autoreactive T cells are not adequately controlled by regulatory T (Treg) cells, and destroy glucose-sensitive beta cells which produce insulin.
The approach to reversing autoimmune irregularity has been theorized and in development in previous studies. "We and other global efforts have known for some time that restoring beneficial Treg cells might halt the abnormal self-reactivity in type 1 diabetes and other autoimmune diseases, but therapies to restore this immune balance have not achieved long-lasting results,” stated Dr. Faustman.
BCG therapy may change current methods to restoring and enhancing immune response. In international studies, repeat vaccinations with BCG have exhibited a unique upregulation of Treg cells. This is due to BCG's ability to permanently activate Treg genes, falling in line with an established history of symbiotic co-evolution between humans and mycobacteria.
“The discovery that BCG restores Tregs through epigenetics — a process that modulates whether or not genes are expressed — is exciting,” Dr. Faustman stated. “This 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."
As phase 1 studies have concluded, Faustman's team is preparing for a 5-year, 150-person phase 2 trial to investigate the potential for repeat BCG vaccination to improve type 1 diabetes in adults with existing disease. Phase 1 long-term follow-up data will be published later this year.
A harmless relative of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, BCG is currently approved for use in tuberculosis prevention and treatment of bladder cancer.
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Kuhtreiber W, Plager S, Kim T, Zheng H, Faustman DL. Permanent epigenetic changes in Treg signature genes of type 1 diabetic subjecgts after in vivo BCG vaccinations. Poster presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego, CA. Poster 1816-P.