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No magic bullets: more setbacks on the road to immune intervention in type 1 diabetes

6 June 2013 (11:33 AM) - Hot Topics, Medical Journals, Drug Watch

It is nearly 30 years since immune intervention with cyclosporin was shown to influence the short-term progression of new-onset type 1 diabetes, and numerous subsequent clinical trials have attempted to find a safer means of beta cell salvage and/or preservation following diagnosis. The challenge they all confront is that the human immune system is a remarkably effective survival mechanism, and is not easily by-passed when it has set its sights on a particular target, even when that target is one of our own tissues.

The immune system has many arms, and its most ancient immune defence system, innate immunity, as also known to work together with acquired immunity in mediating the onset and progression of type 1 diabetes. It was therefore logical for investigators to target Interleukin, one of the key regulators of innate immunity, in recent onset diabetes. Two trials have now been reported jointly in the Lancet. [1] [2]

A Canadian-European trial tested canakinumab, an anti-interleukin-1β antibody, and a European study tried anakinra, an interleukin-1 receptor antagonist. Both agents are widely used in other autoimmune diseases, and proved safe in type 1 diabetes. Unfortunately, both agents had no effect at all on insulin requirements or HbA1c.

The investigators rightly point out that targeting one limb of the immune system in isolation is unlikely to change the course of type 1 diabetes, and that multiple interventions may be needed. Catch-22 however is that the more you intervene, the more likely you are to block other essential immune functions. Magic shotguns will need to be used with care.

References

  1. ^ Bonifacio E. Targeting innate immunity in type 1 diabetes: strike one. Lancet 2013;381:1880-1

  2. ^ Moran A et al. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet 2013;381:1905-15