Reverse Type I Diabetes
A new study reveals that through the use of a generic vaccine that increases the level of a specific immune system modulator can cause the destruction of autoimmune cells that target the insulin-secreting cells found in the pancreas. The result shows the restoration of insulin secretion in patients that suffer from type 1 diabetes. The study was led by Dr Denise Faustman, the director of the Immunobiology Laboratody from MGH (Massachusetts General Hospital). The results of the study were published in the online journal PLoS ONE.
Dr Faustman’s team showed that activating the expression of the TNF (tumor necrosis factor) cured type 1 diabetes is laboratory mice, thus allowing the pancreatic cells to regenerate. Due to the fact that increased amounts of TNF are toxic to human patients, the team used the BCG vaccine (Bacillus Calmette-GuÃ©rin), a vaccine that slowly raises the levels of TNF.
“We believe we have validated in humans the treatment pathway we originally reported in mice and are seeing early evidence of effectiveness. 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”, said Dr Faustman.
The Bacillus Calmette-GuÃ©rin is a generic vaccine that is approved by the FDA (Food and Drug Administration) for use against tuberculosis and bladder cancer. The study led by Dr Faustman is a double-blind Phase I clinical trial. It enrolled six patients who were diagnosed with type 1 diabetes for an average of 15 years. The patients were randomly given either two doses of BCG or two doses of placebo. Six patients without diabetes were also used as a control group for the study. Blood samples from the diabetes patients were compared to those of the control group and the blood samples of 90 other random people (75 patients with diabetes and 15 patients without diabetes). The blood test measured the levels of insulin-autoreactive T cells, of regulatory T cells, of the C-peptide and of an auto-antibody.
The clinical trial lasted for 20 weeks. An increase in the death of insulin-autoreactive T cells and regulatory T cells has been seen in two out of the three participants that were treated with BCG. Furthermore, an increase in the C-peptide levels, which is a marker of pancreatic insulin secretion, was discovered in the patients treated with BCG. One of the patients that was treated with placebo also showed the same response. However, that particular response appeared after a coincidental infection with the Epstein-Barr virus, which is known to activate the TNF expression. The team says there were no notable side effects, whilst also adding that an increase in the dose of BCG could lead to a longer lasting result, thus aiding the restoration of C-peptide secretion and the production of insulin.
“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”, said Dr Paul Burn, who is the chair and director of the Stanford Project and a professor of Pediatrics.
According to recent clinical trials from Italy, the vaccination with BCG could be related to the prevention of brain lesions caused by advanced multiple sclerosis. Advanced MS is an autoimmune disease that is caused by the autoreactive T cells that are vulnerable to the cellular death triggered by TNF. Another Turkish study suggests that repeated BCG vaccination might prevent the onset of diabetes in children, whilst also preventing the formation of autoantibodies. The study published by Dr Faustman is the result of a twenty year quest which started with the understanding of the role of the tumor necrosis factor. Today, after nearly 20 years of research, her team discovered a method to inhibit the T cells responsible for the onset of diabetes.
“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”, said Dr Faustman.