Prevention Research Strategy
A general roadmap for the overall prevention strategy that embraces the concept of a childhood population-based approach is shown below:
JDRF will focus financial and non-financial resources on prevention of the onset of type 1 diabetes in childhood using childhood population-targeted approaches. By leveraging data and biosamples from type 1 diabetes natural history studies, a childhood-onset type 1 diabetes preventive strategy can be developed that takes advantage of current infant-childhood health care practices. Both pre-beta cell autoimmunity and post-beta cell autoimmunity prevention are being targeted based on the concept that pre-beta cell autoimmunity prevention, though more cost effective and ultimately desired, is higher risk and will take longer to deliver than post-beta cell autoimmunity prevention.
JDRF’s pre-autoimmunity prevention strategy focuses on developing preventive vaccines for universal infant/childhood immunization that target:
- Common infectious causes that have been conserved in geographically diverse childhood populations over time. The potential for enteroviral diabetes prevention vaccines will be explored;
- Gut micro-organism-induced immunoregulation, which we hypothesize has been altered due to environmental changes and has led to an imbalance of immunoregulation in the infant and young child to lower the threshold for development of type 1 diabetes; or
- Autoimmune responses to beta cell antigens to induce durable beta cell-specific immunoregulation/immune tolerance. These diabetes vaccines will need to be safe, proven effective, and will not require companion diagnostics in their application. Clinical development of these vaccines may be accelerated by initially conducting clinical trials in genetically very high-risk groups and using prevention of beta cell-specific autoimmunity as a surrogate clinical endpoint for prevention of insulin dependence and type 1 diabetes.
JDRF’s post-autoimmunity prevention strategy focuses on developing childhood population-based:
- Cost effective detection of risk of childhood type 1 diabetes;
- Staging of progression from the onset of autoimmunity to the onset of insulin dependence with prognostic biomarkers and imaging for tailoring interventions;
- Substage-specific interventions to durably prevent the onset of insulin dependence, which include interventions used singly or in combination targeting:a) islet inflammation;
b) beta cell-specific autoimmunity;
c) beta cell stress and survival; and/or
- Development and validation of measurement tools of clinical efficacy of interventions to aid in therapeutic development and evaluation in clinical trials. To accelerate clinical development, trials may be conducted initially in at-risk relatives of individuals with type 1 diabetes and use as their clinical endpoints the prevention of progression to the next stage of type 1 diabetes or reversal of dysglycemia and delay of insulin dependence.
Prevention Research: Top Priority Areas for Fiscal Year 2013
- Discovery and validation of biomarkers to monitor risk and stage progression of T1D.
- Use of clinical biosamples from natural history studies to better characterize disease pathogenesis, heterogeneity, stages, risk scores, and slow and fast progression in the at-risk setting.
- Secondary prevention clinical trials.
- Better characterization of heterogeneity of established T1D.