We believe that targeting both aspects of the immune-endocrine cross-talk is needed to efficiently prevent and treat T1D. We will screen for agents that can decrease beta-cell stress and death and evaluate combination therapies with immunomodulatory drugs to reinstall immune tolerance. With the objective of preventing the early steps of islet autoimmunity, we will focus on non invasive therapeutic strategies (e.g. intranasal administration), which would improve applicability to at-risk but as yet clinically healthy children. In this perspective, we have already launched several clinical studies to screen patients at-risk of T1D in affected families.