Background & Purpose

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PURPOSE

JDRF invites applications to discover or validate mechanisms, processes, and triggers that contribute to human type 1 diabetes (T1D) pathogenesis. Projects funded by this RFA are expected to generate knowledge about early factors that trigger T1D and processes that drive T1D progression. This RFA aims to fund innovative research that will provide insights into mechanisms of disease pathogenesis that will enable future approaches to predict and prevent initiation and progression of T1D.

BACKGROUND

T1D is a complex, chronic autoimmune disease. T1D can be diagnosed at any age, and approximately half of all diagnoses are made in adults. The number of newly diagnosed T1D patients worldwide is accelerating between 3-4% annually. The earliest detectable event in the development of T1D is the appearance of islet autoantibodies in the blood, which denotes beta cell autoimmunity (Stage 1). As T1D progresses, the immune system destroys insulin-producing beta cells in pancreatic islets, leading to dysregulated glucose control (Stage 2) and life-long dependence on exogenous insulin therapy (Stage 3). We do not understand the triggers that impact the development of beta cell autoimmunity (Stages 1/2 T1D) or the progression from Stages 1/2 to clinical T1D (Stage 3). Because of this, there is no cure or method of prevention for T1D.

Several risk factors for developing T1D have been identified. The risk of developing T1D is increased by certain genes, like the inherited susceptibility genes of the HLA family. In addition, non-genetic factors such as an individual’s immune system and environmental influences are believed to impact disease pathogenesis and progression. Studies investigating the role of the immune system in driving T1D have been done, but how immune cell/islet interactions drive T1D is still largely unknown. In addition environmental contributions such as diet, stress-induced changes in metabolism, viral pathogens, and carcinogens need further study in T1D pathogenesis.

This RFA is focused specifically on mechanisms of human T1D disease pathogenesis. There are likely multiple factors that simultaneously contribute to the disease. Research generated from this RFA should contribute knowledge to enable the prevention of T1D through the identification and validation of targets for preventative therapies, informing strategies for effective therapeutic modulation of these targets, and/or development of tools that will allow the identification of patients likely to benefit from preventative therapies.