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Vaccine Prevents and Reverses New-Onset Diabetes

Posted: Thursday, July 03, 2008

A novel microsphere-based vaccine targeting dendritic cells prevents and reverses new-onset autoimmune diabetes in a mouse model, according to a report in the June issue of Diabetes. 

 
Dr. Nick Giannoukakis from the University of Pittsburgh School of Medicine, Pennsylvania said that, "Although we are getting closer to cell-based and DNA therapies for autoimmunity, perhaps our method may not work for everyone."
"Certainly, it will not 'reverse' disease in a person who has had diabetes for more than 5 years (very little beta cell mass is expected in these people)," he cautioned.

Dr. Giannoukakis and associates investigated the efficacy of microspheres carrying antisense oligonucleotides to CD40, CD80 and CD86 to prevent type 1 diabetes and to reverse new-onset disease in the NOD mouse model of diabetes.� The antisense oligonucleotides used in the microsphere-based vaccine were previously shown to render human dendritic cells diabetes-suppressive.

A single injection of the microspheres at a site drained by the pancreatic lymph nodes significantly delayed the onset of diabetes, the authors report, and 8 consecutive injections prevented the onset of diabetes altogether.

Similar studies in NOD mice with established hyperglycemia showed that injection of the microspheres twice weekly for no more than 25 days could reverse new-onset hyperglycemia and maintain the normoglycemic state after vaccine discontinuation.

 
Placebo-treated mice and diabetic controls showed significant insulitis and indistinguishable islet mass, the researchers note, whereas mice treated with the microsphere-based vaccine showed normal islet architecture with an absence of insulitis.
The antisense oligonucleotide-formulated microspheres augmented Foxp3+ regulatory T cells and induced hyporesponsiveness to NOD-derived pancreatic beta-cell antigen without compromising global immune responses to alloantigens and nominal antigens, the investigators found.

"The microspheres will be tested for safety in established type 1 diabetic volunteers as soon as (an ongoing) dendritic cell (DC) phase I study ends," Dr. Giannoukakis said. "Once safety is confirmed for the microspheres, we will then compare the efficacy of both microspheres and the DC to reverse new onset disease and to abrogate the evolution of subclinical type 1 diabetes into full-blown hyperglycemia. This we predict to begin by the end of 2010, early 2011."

"Since both approaches involve immunoregulatory DC, we feared that we could encounter rashes, acute allergy-like symptoms, flu-like symptoms, skin discolorations, and, in the extreme, immune shock-like symptoms or inducement of other autoimmune disease (like thyroiditis, for example)," Dr. Giannoukakis explained. "Thus far, in the ongoing phase I DC study, none of this has occurred, and we do not predict that the microspheres will behave any differently."

He concluded: "Physicians need to be up to date with the basic science literature to understand a lot of the therapeutics now in translational phase. This requires not only an investment in reading, but also an acceptance that dogma is relative and so ever-changing, as basic medical research uncovers the mysteries of how the human body functions and dysfunctions."

Source: Diabetes In Control: Diabetes 2008;57:1544-1555.

 
 
 
 
 
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