In a major breakthrough, published in the Journal of Clinical Investigation in July 2001, Dr. Faustman and her colleagues at MGH cured end-stage diabetic (NOD) mice. In this mouse model of autoimmune diabetes, the Faustman lab’s brief, two-part, non-toxic treatment restored normal blood glucose levels permanently. This achievement was based on previous discoveries in Dr. Faustman's Laboratory on the nature of the autoimmune response and how to specifically eliminate the "bad" (defective) white blood cells in an animal model of type 1 diabetes.

In her previous work, Dr. Faustman identified a “bad” white blood cell in diabetic mice, one with an immune T cell defect, that was responsible for the destruction of insulin-producing beta cells. It is because of this defect
that the cells mature inappropriately and become autoreactive T cells (attacking the body’s own beta cells). Luckily, this same defect also results in a flaw that may allow these T cells to be singled out and destroyed: the autoreactive cells are more susceptible to the effects of a signaling protein, known as TNFalpha, which initiates the process of apoptosis, or cell suicide. In the NOD mouse, Dr. Faustman and colleagues used a drug called Complete Freund’s Adjuvant (CFA), which is the same as a prescription drug for humans called BCG, to raise the levels of TNF in the mice. This eliminated the autoreactive cells.

A second part of the treatment prevented the redevelopment of the disease-producing autoimmune T cells. Immune proteins from normal mice were able to re-educate the T-cells to recognize the pancreatic beta cells as "self", preventing autoimmune cell formation and beta cell destruction. The natural process of beta cell regeneration then cured the diabetes in the mouse experiments. What was most remarkable was that, when the autoimmune disease was eliminated, the pancreas regenerated, thus eliminating the need for use of insulin or a cell transplant.

The MGH research team has evidence that this T cell defect found in diabetic mice is physiologically identical to that found in diabetic humans. In a screening program at the MGH Immunobiology Laboratory under Dr Faustman's leadership, defective T cells have been identified in Type 1 diabetic patients, but not in healthy control subjects. Furthermore, the severity of the T cell defect seems to be directly proportional to the age of diabetes onset. The younger the patient, the greater numbers of defective T cells.

The team has developed and is continuing to develop T cells assays in the laboratory for rapid and accurate analysis of defective cells in patient blood samples, suitable for use in a clinical study. This assay will enable physicians to identify patients who are likely to benefit from the treatment and can also be used to provide evidence of the success of the treatment. This assay is being used in a Phase I human clinical trial that is testing one part of the two part therapy Dr. Faustman and colleagues used to eliminate type 1 diabetes in mice. Instead of CFA (used in the mouse studies), the human trial will test a generic drug called bacillus Calmette-Guerin (BCG), which is the human grade equivalent of CFA. BCG is already used for other diseases, such as tuberculosis (TB) and some cancers, and has an excellent safety profile in humans. BCG causes the body to produce TNF, which the researchers at MGH hope will lead to the selective destruction of the autoreactive T cells that are present in type 1 diabetes.

This human trial, which began in January 2008, is part of MGH’s program of research aimed at developing a curative therapy for human Type 1 diabetes. It will evaluate whether treatment with BCG vaccination can eliminate the abnormal white blood cells in patients with Type 1 diabetes. More information about this trial is available at: www.faustmanlab.org.