Robert A Press, M.D., Ph.D.

Clinical Professor; Chief Med OffNYU Langone Medical Center
Department of Medicine (Chief Medical Officer)

Clinical Addresses

530 FIRST AVENUE, 4G
NEW YORK, NY 10016
Hours: Tue. 8 - 12
Phone: 212-263-7229
Fax: 212-263-8630

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Board Certification

1976 — Ab Internal Medicine - Internal Medicine
1976 — Internal Medicine

Education

1973 — New York University School of Medicine, Medical Education
1973-1975 — Beth Israel Hospital (Medicine), Residency Training
1975-1976 — NYU Medical Center (Medicine), Residency Training
1976-1978 — Montefiore Medical Center (Infectious Diseases), Clinical Fellowships

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Abstract

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2012;7(8):e41756. doi: 10.1371/journal.pone.0041756. Epub 2012 Aug 8.

Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes.

Faustman DL, Wang L, Okubo Y, Burger D, Ban L, Man G, Zheng H, Schoenfeld D, Pompei R, Avruch J, Nathan DM.

Source

The Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. faustman@helix.mgh.harvard.edu

Abstract

BACKGROUND:

No targeted immunotherapies reverse type 1 diabetes in humans. However, in a rodent model of type 1 diabetes, Bacillus Calmette-Guerin (BCG) reverses disease by restoring insulin secretion. Specifically, it stimulates innate immunity by inducing the host to produce tumor necrosis factor (TNF), which, in turn, kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration.

METHODOLOGY/PRINCIPAL FINDINGS:

Translating these findings to humans, we administered BCG, a generic vaccine, in a proof-of-principle, double-blind, placebo-controlled trial of adults with long-term type 1 diabetes (mean: 15.3 years) at one clinical center in North America. Six subjects were randomly assigned to BCG or placebo and compared to self, healthy paired controls (n = 6) or reference subjects with (n = 57) or without (n = 16) type 1 diabetes, depending upon the outcome measure. We monitored weekly blood samples for 20 weeks for insulin-autoreactive T cells, regulatory T cells (Tregs), glutamic acid decarboxylase (GAD) and other autoantibodies, and C-peptide, a marker of insulin secretion. BCG-treated patients and one placebo-treated patient who, after enrollment, unexpectedly developed acute Epstein-Barr virus infection, a known TNF inducer, exclusively showed increases in dead insulin-autoreactive T cells and induction of Tregs. C-peptide levels (pmol/L) significantly rose transiently in two BCG-treated subjects (means: 3.49 pmol/L [95% CI 2.95-3.8], 2.57 [95% CI 1.65-3.49]) and the EBV-infected subject (3.16 [95% CI 2.54-3.69]) vs.1.65 [95% CI 1.55-3.2] in reference diabetic subjects. BCG-treated subjects each had more than 50% of their C-peptide values above the 95(th) percentile of the reference subjects. The EBV-infected subject had 18% of C-peptide values above this level.

CONCLUSIONS/SIGNIFICANCE:

We conclude that BCG treatment or EBV infection transiently modified the autoimmunity that underlies type 1 diabetes by stimulating the host innate immune response. This suggests that BCG or other stimulators of host innate immunity may have value in the treatment of long-term diabetes.