A novel therapy for diabetes

The discovery of regulatory T cells (Tregs) as the key population that maintains peripheral tolerance has significantly enhanced our understanding of autoimmune diseases. Emerging evidence indicates that Tregs are actively implicated in diabetes and play an instrumental role in limiting chronic inflammatory diseases, such as asthma.

In diabetes, the immune-mediated destruction of pancreatic beta cells suggests that Tregs are inactive and could be stimulated to stop disease onset or progression. With this in mind, researchers on the EU-funded 'Ultra-low dose of IL-2 for the treatment of recently diagnosed type 1 diabetes' (DIABIL-2) project propose to use Interleukin-2 (IL-2) as a means of stimulating Tregs in diabetic patients.

Previous work by the consortium has shown that using IL-2 in a diabetic mouse model can prevent and cure diabetes. In humans, IL-2 administration is safe and activates Tregs, and it can treat hepatitis C-mediated symptoms.

DIABIL-2 aims to extend these findings and test an ultra-low dose of IL-2 in a phase IIb clinical trial with newly diagnosed type 1 diabetes (T1D) patients. The study will be conducted in different centres across Europe and will include patients stratified by age.

During the first part of the project, partners have finalised the necessary documentation for obtaining clinical trial approval. IL-2 has been produced at good manufacturing practices-level in a lyophilised form that is anticipated to reduce the number of patient hospital visits. A central laboratory has also been selected for handling patient samples and managing data.

A significant part of the project has been dedicated to the analysis of patient Tregs. Researchers wish to determine the methylation status of the master regulator of Treg development and function, FOXP3.

The success of the DIABIL-2 approach in stopping autoimmune pancreatic beta cell destruction could revolutionise diabetes treatment and management. Especially with respect to childhood T1D, this could alleviate disease symptoms and improve the quality of life of young patients and their families.