anti-CD20 and anti-CD3 by Hu and Wen at Yale

Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes

Abstract: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell- and B cell-directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve the therapeutic efficacy remains to be explored. Herein we show that the combined treatment with intravenous anti-human CD20 (hCD20) and oral anti-CD3 significantly delayed diabetes development in pre-diabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reversed diabetes in more than 60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B cell depletion therapy synergistically enhanced the suppressive function of Treg. Interestingly, the oral anti-CD3 treatment induced a fraction of IL-10-producing CD4 T cells in the small intestine through IL-10 and IL-27-producing dendritic cells. Thus, our findings demonstrated that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell-directed therapy for type 1 diabetes.

Intestinal microbes by Danska at Hospital for Sick Children and the University of Toronto

By exposing female mice to the gut bacteria of a healthy adult male, researchers were able to prevent the females from developing type 1 diabetes, an autoimmune disorder. ... the treatment changed the levels of testosterone in female mice, which typically develop type 1 diabetes at a higher rate than their male counterparts.

Abstract: http://www.sciencemag.org/content/early/2013/01/16/science.1233521.abstract

Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. Here, we demonstrate a direct interaction between sex hormones and early life microbial exposures on the control of autoimmunity in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.

Encapsulated Embryonic Stem Cells by ViaCyte

Quotes:

ViaCyte’s artificial pancreas is grown from embryonic stem cells. It contains the insulin-producing “islet” or “beta” cells destroyed in Type 1, or insulin-dependent diabetes.  

The device has eliminated diabetes symptoms in diabetic mice and rats. 

ViaCyte’s islet cells are encapsulated in an implanted medical device. The cells are separated from the body by a semipermeable barrier that allows the cells to derive nutrients from the blood and secrete insulin, but shields the cells from the body’s immune system. This prevents the body from rejecting the cells, and presumably would eliminate the need for immunosuppressive drugs given to transplant recipients.

News: http://www.utsandiego.com/news/2012/oct/27/tp-viacyte-gets-101m-for-stem-cell-work/

Ectopic PDX-1 expression in liver ameliorates type 1 diabetes.

Using the model of cyclophosphamide-accelerated diabetes in non-obese diabetic (CAD-NOD) mice, we report that recombinant adenovirus mediated PDX-1 gene therapy, ameliorates hyperglycemia in CAD-NOD mice. Our data demonstrate that 43% of the overtly diabetic CAD-NOD mice treated with Ad-CMV-PDX-1 became normoglycemic and maintained a stable body weight.

http://www.ncbi.nlm.nih.gov/pubmed/17383157

http://www.deepdyve.com/lp/elsevier/ectopic-pdx-1-expression-in-liver-ameliorates-type-1-diabetes-YQBPZV2yBC

Newer:
http://www.biomedreports.com/2012061597242/using-a-diabetes-patients-own-liver-cells-as-a-novel-source-of-insulin.html

Quotes:

A novel approach to this problem is currently being pursued by a small biotech company named Orgenesis, which initiated its approach by asking the following question: What if a diabetes patient's own cells-extracted from his or her own mature tissue-could be made to produce insulin, secreting the compound automatically when needed? This particular variety of cell therapy is a form of what has been dubbed "autologous cell replacement."

Orgenesis has successfully tested its technology in mice, rats and pigs, and is working toward initiating clinical trials in humans.   

ISO-1 by Al-Abed at Feinstein Institute

Quote:

Dr. Al-Abed developed a potent inhibitor of MIF [called ISO-1] that has been shown to be effective in preclinical studies of type 1 diabetes and sepsis, and is now designing clinical trials.

Press Release: http://www.feinsteininstitute.org/Feinstein/Laboratory+of+Medicinal+Chemistry

Intestinal Parasite Infection by Mishra and Gause at University of Medicine and Dentistry of New Jersey

Yes, they infected NOD mice with an intestinal parasite, and this prevented later development of type-1.  Here's the quote from the press release:

shows that a two-week infection with the intestinal worm H. polygyrus (cured using oral drugs) prompted T cells to produce the cytokines interleukin (IL)-4 and IL-10, which acted independently to provide lasting protection against TID in mice

Abstract: http://www.nature.com/mi/journal/vaop/ncurrent/full/mi201271a.html
News Article: http://www.sciencedaily.com/releases/2012/07/120719103244.htm

Macrophages by Harris at Karolinska Institutet

Quote from the abstract:

Clinical therapeutic efficacy was assessed after adoptive transfer in NOD T1D, and after a single transfer of M2r macrophages, >80% of treated NOD mice were protected against T1D for at least 3 months, even when transfer was conducted just prior to clinical onset.

Quote from the news article:

At the end of the follow-up period only 25% of the mice receiving the cytokine-treated macrophages had developed Type 1 diabetes, while 83% of the control groups had become sick. 

"The cell therapy was initiated just 2 weeks before mice developed clinical diabetes", says Dr Harris. "At this stage few insulin-producing beta cells remain in the pancreas, yet we were able to protect these so that the mice never developed diabetes. Such a successful late-stage intervention has never previously been reported and is a significant result of our study. At the time of their clinical Type 1 diabetes diagnosis, most human individuals have already lost most of their insulin-producing beta cells."

News: http://bulletin.sciencebusiness.net/news/75792/Karolinska-researchers-prevent-mice-from-developing-diabetes
Abstract: http://diabetes.diabetesjournals.org/content/early/2012/06/20/db11-1635.abstract