Sunday, October 28, 2012

Encapsulated Embryonic Stem Cells by ViaCyte

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.


Friday, September 21, 2012

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.



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.   

Thursday, August 9, 2012

ISO-1 by Al-Abed at Feinstein Institute

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.

Thursday, July 19, 2012

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

News Article:

Thursday, June 28, 2012

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."


Wednesday, June 27, 2012

Stem Cells (hESCs) by Rezania and Kieffer at University of British Columbia and BetaLogics

I'm not sure I should count this as a "cured in mice".  Basically the researchers took mice that had a compromised immune system, and then made them diabetic by poisoning their pancreas, and then cured them by implanting human embryonic stem cells (hESCs).  I think this proves that they know the recipe to turn hESCs into functional beta cells (a huge advance in itself), but it is not a cure for real type-1 diabetes, because the autoimmune attack would still kill off the new beta cells.  The mice used in this experiment did not have autoimmune (type-1) diabetes.

From the abstract:
As graft-derived insulin levels increased over time, diabetic mice were weaned from exogenous insulin and human C-peptide secretion was eventually regulated by meal and glucose challenges.

Press release:
News article:

Monday, June 25, 2012

Non-Depleting Antibodies by Yi and Tisch at University of North Carolina

From the news article:

In some of the recently diagnosed NOD mice, blood sugar levels returned to normal within 48 hours of treatment. Within five days, about 80 percent of the animals had undergone diabetes remission, reversal of clinical diabetes. 
"The protective effect is very rapid, and once established, is long-term," [Tisch] said. "We followed the animals in excess of 400 days after the two antibody treatments, and the majority remained free of diabetes. And although the antibodies are cleared from within the animals in 2-3 weeks after treatment, the protective effect persists." The study showed that beta cells in the NOD mice had been rescued from ongoing autoimmune destruction.

I was asked if this is new concept or not.  Basically, I think that, in science, everything is based on work done before, so deciding that something is "new" or not usually involves arguing about the definition of "new", and is a waste of time.  Everything has some new parts and some old parts.

However, I will say that work in non-depleting antibodies targeting CD4 and CD8 to cure or prevent type-1 diabetes has been going on for about 20 years.  (Pubmed references from 1992, so the research actually has gone on longer than that.)  So from that point of view, I don't think this basic approach is completely novel, but I'm hoping these researchers are using a different antibody than has been used in the past, and that they will be more successful in humans than previous attempts.


Much older stuff:

Wednesday, May 9, 2012

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

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.

News article:

Monday, May 7, 2012

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:

Wednesday, April 11, 2012

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

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:

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.)

Friday, March 16, 2012

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.


Saturday, March 10, 2012

CD40 inhibitory peptide by Wagner at University of Colorado


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:

Related grant:
Related research:

Thursday, March 8, 2012

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:

Tuesday, February 21, 2012

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


Tuesday, February 7, 2012

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.

Monday, January 30, 2012

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


Saturday, January 28, 2012

Protein and Nanoparticle by Santamaria at Parvus

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:

Sunday, January 1, 2012

Catenarin by Shen at Taiwan

Quote from Abstract:
Overall, the data demonstrate the preventive effect and molecular mechanism of action of catenarin on T1D, suggesting its novel use as a prophylactic agent in T1D.

Full paper: