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.

bone marrow and cell grow factors by Zeng at University of Florida

Quote:

a new combination therapy that reverses established Type 1 diabetes in mice. ... The two-step regimen involves bone marrow transplantation and substances that promote the growth of cells that produce insulin, the sugar-regulating hormone that is missing in people who have Type 1 diabetes.

Source: http://news.ufl.edu/2012/05/09/diabetes-reversal/
News article: http://www.bloomberg.com/news/2012-05-09/immune-cell-therapy-cures-diabetic-mice-researchers-find.html

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

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/

anti-CD98hc by Lian at University of Tokushima

Paper Title: Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice.

Quote from the Abstract:

Injection of the anti-CD98hc [monoclonal antibody] completely prevented the onset of cyclophosphamide-induced diabetes in NOD mice. Treatment of diabetic NOD mice with anti-CD98hc reversed the diabetic state to normal levels, .... Furthermore, treatment of diabetic NOD mice with CD98hc small interfering RNA resolved T1D. These data indicate that strategies targeting CD98hc might have clinical application for treating T1D

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22291182

Protein and Nanoparticle by Santamaria at Parvus

Quote:

Parvus, which is basically Santamaria, Coggins and Jord Cowan and two of them still have day jobs has spent the last 18 months testing the treatment on mice.
With 70 per cent to 80 per cent of the animals permanently free of diabetes after receiving the injections, according to Coggins, the company is now looking to raise $30 million to move to clinical trials.
Even the 20 to 30 per cent of mice who relapse see the disease disappear after another round of treatment, Coggins said.

News article: http://www.calgaryherald.com/touch/story.html?id=6064209

Encapsulated Beta Cells by Nuvilex at SG Austria

Quote from the press release:

Nuvilex, Inc.announced today their affiliate SG Austria and partners have successfully treated diabetes in an established, recognized animal model utilizing live encapsulated cells.

The introduced cells responded to elevated blood sugar levels by producing insulin, alleviating the symptoms of diabetes. Moreover, encapsulated cells remained viable and responsive for many months.

Press release: http://www.marketwatch.com/story/nuvilex-and-sg-austria-introduce-revolutionary-treatment-for-diabetes-utilizing-live-cell-encapsulation-technology-2011-12-06

Pig to Rat Embryonic Transplant by Hammerman at Washington University School of Medicine

Press Release: http://medicalxpress.com/news/2011-11-pig-primate-transplants-diabetes.html

Note that the 15-Nov-2011 date refers to experiments on Monkeys that did not lead to a cure, but this press release also referred to previous experiments on rats that did lead to a cure for them.  Since I didn't have the rat cure before, I'm counting this as the rat cure.

Quotes:

Researchers at Washington University School of Medicine in St. Louis transplanted clusters of embryonic pig cells destined to become insulin-producing islet cells into three diabetic rhesus macaques. The macaques “adopted” the pig cells as their own, without the need for powerful immune suppression drugs to prevent rejection, the researchers report in the current issue of Organogenesis.

The new study builds on earlier research in rats, reported by the same group last year in the American Journal of Pathology. In that study, the researchers used the same two-step approach to cure diabetes in rats. Unlike the macaques, rats that received both embryonic cell and islet cell transplants from the pigs could produce enough insulin to adequately control their blood sugar.

Glyphosine by Michels at Barbara Davis Centre for Childhood Diabetes

A specific molecule that can prevent the development of type 1 diabetes in mice has a similar effect on human cells from diabetic patients, according to researchers at the University of Colorado School of Medicine.

http://www.ncbi.nlm.nih.gov/pubmed/22043012
http://news.bioscholar.com/2011/11/promising-new-compound-to-prevent-type-1-diabetes-identified.html

GABA by Prud’homme at St. Michael’s Hospital in Toronto

News coverage: http://fftimes.com/node/243716

Quotes:

A natural chemical generated by the same cells that produce insulin in the pancreas has been found to not only prevent Type 1 diabetes in mice but reverse the condition, according to a new study.
Dr. Qinghua Wang and Dr. Gerald Prud’homme of St. Michael’s Hospital in Toronto led a team of international researchers in the study. Findings were published yesterday in the journal Proceedings of the National Academy of Sciences.

Gene Therapy and interleukin-10 by Chan at Baylor

However, when the researchers combined the gene therapy with interleukin-10 into a single intravenous injection, the treatment showed a complete reversal of diabetes in half of the mice during more than 20 months' follow-up. Although the therapy did not reverse autoimmunity throughout the body, it protected the new beta cells from the local destructive effect of autoimmunity, Chan explained.


http://english.farsnews.com/newstext.php?nn=8904060488

Gene Therapy targeting 12-Lipoxygenase at Eastern Virginia Medical School's Strelitz Diabetes Center

Studies have shown that deleting the gene that produces 12-LO can stop Type 1 diabetes in mice. Studies of donated human beta cells have allowed the researchers to confirm that the enzyme is the cause of beta cell destruction from inflammation. "We've now confirmed that 12-LO is a relevant target in humans, particularly in the pancreas, and will help lead to new therapies," says the EVMS researchers. 

http://www.emaxhealth.com/1020/23/35409/targeting-newly-identified-enzyme-could-cure-type-1-diabetes.html

Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1102

Sertoli cells by Fallarino at University of Perugia

Quote:

We report that isolated neonatal porcine Sertoli cells , administered alone in highly biocompatible microcapsules, led to diabetes prevention and reversion in the respective 88 and 81% of overtly diabetic (nonobese diabetic [NOD]) mice, with no need for additional beta cell or insulin therapy. The effect was associated with restoration of systemic immune tolerance and detection of functional pancreatic islets that consisted of glucose-responsive and insulin-secreting cells.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19822646
Paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768846/

lisofylline and exendin-4 by Yang at University of Virginia

Quote:

in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance β-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. 

Abstract: http://www.sciencedirect.com/science/article/pii/S0006291X06007066