The collaborative project DIAPREPP specifically addresses the call FP7 Cooperation Work Programme: Health-2007-2.4.3-1 Early processes in the pathogenesis of type 1 diabetes and strategies for early prevention. The coordinator is Ezio Bonfacio, Dresden, Germany.
The earliest currently identifiable process in the pathogenesis of type 1 diabetes (T1D) is the appearance of islet autoantibodies in very young children. It is poorly understood how to prevent autoimmune T1D as the etiology and pathogenesis of the islet auto-immunization has not been clarified. It needs to be determined if the development of islet autoantibodies are preceded by metabolic abnormalities, cell-mediated autoimmunity, or both. DIAPREPP will focus on the early auto-immunization against islet antigens, in particular to disclose events preceding current autoantibody markers. The concept is that events prior to auto-immunization govern the likelihood and 'signature' of immunization, which in turn determines progression to disease. The overall objective is to determine mechanisms of islet autoantigen immunization. In a truly collaborative manner, and through five workpackages in addition to three dedicated to dissemination, training, and management, DIAPREPP will
1. Provide a unique set of clinical material that includes a case-control cohort representative of the world's largest studies of pre-T1D, with follow-up and samples from birth, and pancreatic islets and lymph nodes from patients;
2. Investigate the effects of environmental exposure to infections on islet cells and immune cells;
3. Perform extensive metabolomic analysis of pre-autoimmune samples and in relevant animal models to test mechanistic hypotheses of auto-immunization;
4. Carry out detailed analyses of early autoimmune responses with a special focus on autoreactive CD8+ T cells;
5. Apply findings to ongoing prevention studies.
Work Package 5: Clinical Translation
WP5 is concerned with clinical translation and application of the knowledge gained from WP1-4 that will be translated into the development of prototype tests for commercialization and standardization in international settings, application of these tests and findings in important international intervention studies, and accordingly address possible prevention strategies related to WP2-4.
To establish a model T1D prevention plan and a handbook on how to translate new knowledge obtained from other work packages (WP 1–4) of DIAPREPP into clinical trials aiming at prevention or finding cure therapies for T1D. This aim will be complementary and linked to other international efforts focusing on T1D prevention such as TrialNet and Immune Tolerance Network (ITN).
Areas of concern
Set criteria for subject selection for clinical prevention trials T1D.
Identify pathways in T1D pathogenesis that may be modulated to halt autoimmune insult or retard disease progression prior to clinical onset.
Design strategies and cohesive infrastructure for implementation of clinical trials.
Prepare assays for subject selection and monitoring.