Hyperbaric Oxygen by Pileggi at Diabetes Research Institute

Hyperbaric Oxygen treatment is basically putting people in a chamber with extra oxygen at higher pressure. In these experiments, animals were put in 100% oxygen at twice normal atmospheric pressure.

Quotes from the abstract:

Spontaneous diabetes incidence reduced from 85% in controls to 65% in  [hyperbaric oxygen treatment]  (P = 0.01). ... Cyclophosphamide-induced diabetes onset was reduced from 85.3% in controls to 48% after [hyperbaric oxygen treatment] (P < 0.005) and paralleled by lower insulitis. 

Quote from the news article:

In mice, the treatment caused changes in the immune system's response to newly developing diabetes, and reduced the risk of diabetes between 20 and 40 percent. In the mice that still developed diabetes, the hyperbaric therapy delayed disease progression, the investigators found.

News article: http://health.usnews.com/health-news/news/articles/2012/05/11/oxygen-therapy-slows-type-1-diabetes-in-mice-study-says
Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22566533

proinsulin autoantigen, IL-10, and anti-CD3 by Mathieu at KU Leuven

Quote:

Our intervention effectively reverted diabetes in newly diagnosed diabetic NOD mice, with a success rate seldom approached in NOD mice,” the authors conclude. “The therapy allowed us to exploit lower doses of anti-CD3 (ideally to circumvent side effects and undesired reactions) in combination with other interventions to enhance therapeutic efficacy. In particular, our combination therapy using L. lactis expressing PINS and hIL10 and low-dose anti-CD3 preserved functional β cell mass, resolved severe insulitis

And here was another interesting tid-bit:

Interestingly, the team reports, there was no evidence that the L. lactis-anti-CD3 therapy actually triggered beta-cell proliferation. Rather, it seemed to enable regranulation or reactivation of beta cells that had been deactivated by diabetes-related immune inflammation. This suggests that the treatment may only work when there are enough potentially functional beta cells present to start with.

News coverage:
http://www.genengnews.com/gen-news-highlights/engineered-gut-bacteria-reverse-type-1-diabetes-in-experimental-mice/81246608/
Abstract: http://www.jci.org/articles/view/60530#sd

This mouse cure is combining three different treatments and two different delivery systems, so they have got a lot going on.

The anti-CD3 drug is given by injection, so that is standard.  However the proinsulin and the IL-10 is given by genetically modifying a bacteria, and then putting that bacteria in the mouse's gut.  This avoids the problem where the proteins in proinsulin and IL-10 are digested.  Instead they are generated by bacteria right where they are absorbed into the blood stream.

As for the treatments, it's "one of everything":

• Anti-CD3 is an immune system modulator (This drug has been tried extensively in the past, and looked good early on, but failed in phase-III human tests.)
• IL-10 lowers inflammation and lowers the action of part of the immune system called NK cells. (NK "natural killer" cells is part of the immune system, but completely different than the T cells and B cells that most anti-type-1 treatments target.  Obviously, inflammation is an approach which just became popular in the last 4-7 years, and has not panned out as yet.)
• Pro-insulin is an antigen specific attempt to train the immune system not to self attack.  (Like giving peanut proteins to people allergic to peanuts.)

Interleukin-35 by Bettini at St. Judes

Title: Prevention of Autoimmune Diabetes by Ectopic Pancreatic β-Cell Expression of Interleukin-35

Quotes from Abstract:

Interleukin (IL)-35 is a newly identified inhibitory cytokine used by T regulatory cells to control T cell–driven immune responses. ...

Nonobese diabetic RIP-IL35 transgenic mice exhibited decreased islet infiltration with substantial reductions in the number of CD4+ and CD8+ T cells, and frequency of glucose-6-phosphatase catalytic subunit–related protein-specific CD8+ T cells. ...

[This] led to substantial, long-term protection against autoimmune diabetes ... 

These data present a proof of principle that IL-35 could be used as a potent inhibitor of autoimmune diabetes and implicate its potential therapeutic utility in the treatment of type 1 diabetes.

Abstract: http://diabetes.diabetesjournals.org/content/early/2012/03/13/db11-0784.short

CD40 inhibitory peptide by Wagner at University of Colorado

Quotes:

Wagner isolated the specific T-cells that attack the pancreas and cause most cases of Type 1 Diabetes. The research team has developed a drug that attacks those bad cells. 

It’s having an impressive effect on mice. The drug is not only preventing mice from developing diabetes, it’s also reversing the effects of diabetes in mice that already have the disease.

News article: http://denver.cbslocal.com/2012/03/09/cu-researchers-find-cure-for-type-1-diabetes-in-mice/

Related grant: http://www.diabetes.org/news-research/research/research-database/cd40-as-a-biomarker-in-type-1-diabetes.html
Related research: http://www.jleukbio.org/content/84/2/431.abstract

XMetA by Bhaskar at XOMA

XMetA is the first antibody specific for the insulin receptor shown to correct hyperglycemia in a mouse model of diabetes. Results of a study conducted by XOMA and confirmed by investigators at the University of California, San Francisco, demonstrate that XMetA has the potential to be a novel, long-acting agent for the control of blood glucose levels in patients with diabetes.
The study by Bhaskar, et al. demonstrated that XMetA markedly reduced elevated fasting blood glucose levels and normalized glucose tolerance in mice experimentally rendered diabetic. After six weeks of treatment, there was a statistically significant reduction in hemoglobin A1c levels in animals treated with XMetA compared to controls (p < 0.05). In addition, elevated non-HDL cholesterol levels were improved relative to control mice (p < 0.05). Hypoglycemia and weight gain were not observed during this study, nor was proliferation of cell growth.


Press Release: http://www.sciencecodex.com/first_allosteric_insulin_receptoractivating_antibody_to_improve_glycemic_control_in_vivo-87483
Abstract: http://www.ncbi.nlm.nih.gov/pubmed?term=Bhaskar%20XMetA

Hepatic Insulin by Elsner at

The plan for this research was to genetically engineer a virus to create insulin, and then inject that virus into the liver of diabetic animals.  The result was normal BG for the one year duration of the trial.

Title: Reversal of Diabetes Through Gene Therapy of Diabetic Rats by Hepatic Insulin Expression via Lentiviral Transduction

Quotes from Abstract:

• Within 5–7 days after the virus injection of 7 × 109INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. 
• This glucose lowering effect remained stable for the 1 year observation period. 
• Human C-peptide as a marker for hepatic release of human insulin was in the range of 50–100 pmol/ml serum.
• This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach.

Two different types of animals were used:

• autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) 
• streptozotocin-diabetic rats

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22354377

Brown Adipose Tissue Transplant by Gunawardana at Vanderbilt University

Title: Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

Quote from the abstract:

Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) ... BAT transplants result in euglycemia, normalized glucose tolerance, reduced tissue inflammation, and reversal of clinical diabetes markers such as polyuria, polydipsia, and polyphagia.

Abstract: http://diabetes.diabetesjournals.org/content/61/3/674.short

News coverage: http://news.vanderbilt.edu/2012/03/fat-as-diabetes-treatment/