The clinical potential of antigen-specific therapies in type 1 diabetes – Experience from the Novo Nordisk T1D R&D Center
Ken T. Coppieters1, Birgit Sehested Hansen2, and Matthias G. von Herrath1
1 Type 1 Diabetes R&D Center, Novo Nordisk Inc., Seattle, WA, USA
2 Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark
Abstract
In type 1 diabetes (T1D), pancreatic beta cells are attacked by the immune system which in turn leads to a loss of beta cells and thereby endogenous insulin secretion. The desirable therapeutic outcome for autoimmune diseases is the restoration of immune tolerance in order to prevent or curb organ damage. Past trials with immune suppressive drugs highlight the fact that T1D is in principle a curable condition. However, the bar in terms of drug safety in T1D is set particularly high due to the predominantly pediatric population and the excellent prognosis associated with modern exogenous insulin therapies. Thus, there is general consensus that chronic immune suppression is associated with unacceptable long-term safety risks. Immune modulatory biologicals, on the other hand, have recently failed to confer significant protection in phase 3 trials. In this review article, we will argue that the concept of antigen-specific tolerization may offer a unique strategy to safely induce long-term protection against T1D.
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