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.)