Single-drug approaches to treat type 1 diabetes (T1D) have so far yielded only modest results: just a handful of biologics have been able to transiently delay pancreatic beta cell destruction. As such, creating long-term, sustained improvements in T1D may require multiple agents combined in strategic ways. Data from the first combination study from The Immune Tolerance Network (ITN) Type 1 Diabetes Preclinical Consortium was published last week in PLoS ONE alongside data from the La Jolla Institute for Allergy and Immunology (LIAI) (see here).
The study tested a novel combination of anti-CD20, an antibody that targets B cells, with two forms of insulin antigens*. Anti-CD20 has previously shown some therapeutic benefit in patients with recently-diagnosed T1D, and the goal of this research was to test whether these positive effects could be enhanced by the addition of antigen-specific therapy (insulin). Despite sound rationale for this therapy combination, the data revealed that the combination was unable to reverse T1D in the T1D mouse model system. These results highlight the difficulties and complexities in identifying effective combination regimens for type 1 diabetes. By evaluating promising combination therapies in animal models, the consortium hopes to identify and advance the most promising T1D combination therapies to clinical trials more quickly.
The ITN T1D Preclinical Consortium is a joint effort with JDRF that consists of four, independent, geographically diverse laboratories with the goal of generating reproducible data using a single protocol and standardized operating procedures. This consortium will help address the need for coordinated, pre-clinical screening of strategic combinations of agents to demonstrate safety and efficacy before moving into clinical studies.
*The anti-CD20 plus oral insulin study was conducted by the ITNs Type 1 Diabetes Preclinical Consortium. The anti-CD20 plus proinsulin-expressing DNA vaccine study and associated mechanistic work was conducted by the La Jolla Institute for Allergy and Immunology, a member laboratory of the consortium, independent of the consortium’s efforts.