February 21, 2013

Unlocking Diabetes with a Combination Therapy

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combinationsA combination therapy was shown to successfully deter the progression of Type 1 diabetes in recently diagnosed people. The study was published in PLoS ONE

Rituximab  is a drug that destroys cells that have CD20 on their surface. CD20 causes cells to become less responsive to insulin.  The genius of Rituximab is that it can selectively destroy or protect cells from immune destruction.

Rituximab along with an anti-CD3 antibody was shown to protect newly diagnosed T1D patients by increasing their C-peptide levels.  Anti-CD3 antibodies are an immune suppressing drug that attaches to the surface of certain T-cells to impede their ability to target healthy cells.

Anti-CD3 treatments can affect immune responses by inducing immune regulation. Recent studies have shown that a single course of treatment can lead to preservation of insulin production in patients with new-onset T1D for even beyond 1 yr after treatment.

The combination therapy of insulin and anti-CD3 antibody was more protective of beta cells than either therapy alone, Anti-CD20 alone produced brief B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone was also ineffective. Rituximab targets human CD20 causing rapid and specific B cell depletion.

A combination therapy with anti-CD20, such as Rituximab, and either oral insulin or proinsulin does not protect hyperglycemia in NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention.

The verbiage in this study is hard to clearly identify the therapy combination that works best. This may be a padlock to Pandora’s Box.  Or this may be a hint which way to pursue in studies. Either way, it’s showing promise on several different approaches but it’s a matter of finding the right combination to unlock the door.

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