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.

Sources:
http://www.sciencedaily.com/releases/2012/07/120706013709.htm
http://diabetes.diabetesjournals.org/content/early/2012/06/25/db12-0098

Much older stuff:
http://onlinelibrary.wiley.com/doi/10.1002/eji.1830220735/abstract
http://www.freepatentsonline.com/5670150.html

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.)