Following is the phase I abstract of Dr Faustman's BCG research to cure( reverse) diabetes
type 1. The full research paper will be available in next weeks.
Phase I is safety phase with very low doses. The abstract is very promising considering this is only phase I trial.
BCG Treatment of Long-Term Type 1 Diabetics
DENISE L. FAUSTMAN, LIMEI WANG, YOSHIAKI OKUBO, DOUGLAS E. BURGER, LIQIN BAN, GUOTONG MAN, HUI ZHENG, DAVID SCHOENFELD, RICHARD POMPEI, JOSEPH AVRUCH, DAVID M. NATHAN
Charlestown, MA, Boston, MA
No targeted immunotherapies exist for reversing advanced type 1 diabetes. Bacillus-Calmette-Guerin (BCG), which induces release of tumor necrosis factor (TNF), has been used successfully in rodent models to reverse disease by specifically removing autoreactive T cells and unleashing pancreas regeneration to restore long-term normoglycemia. In murine models of type 1 diabetes, this therapeutic intervention is unique in removing beta-cell autoimmunity and improving glycemia even in animals with near complete eradication of beta-cell function, and not just in new onset diabetes.
In this proof-of-principle, phase I trial, we treated adult patients with long-term type 1 diabetics with BCG, a non-virulent genetic vaccine, to determine whether BCG depletes the disease-causing autoimmune cells and identify any pancreatic beta-cell responses. We randomly assigned patients with long-term type 1 diabetes (mean 15-years duration) to repeated BCG vaccinations (n=3) or placebo (n=3) in this 20-week double-blinded placebo-controlled trial and compared them to subjects without diabetes (n=6). We measured blood samples for autoreactive T cells, TREG cells, GAD autoantibodies, and C-peptide, a marker of insulin secretion. Another group of patients with type 1 diabetes (n=58) and nondiabetic (n=17) subjects served as reference subjects for the T cell and other assays. BCG-treated patients and one placebo-treated patient who unexpectedly developed an acute Epstein-Barr virus infection, another known inducer of TNF, exclusively showed transient increases in the number of circulating dead autoreactive T cells against insulin. In two of the BCG subjects and the EBV-infected subject, C-peptide levels rose transiently above baseline levels to a statistically significant extent in comparison to longitudinally followed C-peptide in reference subjects.
BCG-treatment or EBV-infection transiently modified the autoimmunity that underlies even advanced type 1 diabetes, suggesting that similar therapy may have value in the treatment and even reversal of advanced type 1 diabetes. Larger trials are necessary to extend these results and identify the most effective doses and frequency of BCG treatment.
Clinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its Complications