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Combination therapy to prevent type 1 diabetes

Combination therapy to prevent type 1 diabetes

PhD project

Effective antigen-specific therapies that prevent type 1 diabetes have not yet been developed, and data suggest that antigen-specific therapy on its own may not be effective if autoimmunity is already established. We hypothesise that islet inflammation fuels the development of effector memory T cells, and that if this is controlled by immunotherapy, such as JAK inhibitors, antigen-specific therapy will be successful. To test this, we have used mice generated in the lab that have inducible expression of proinsulin in antigen presenting cells under control of the MHC class II promoter, combined with JAK1/JAK2 inhibitor treatment to block cytokine signalling. Preliminary experiments show that short-term JAK inhibitor treatment between 2 and 4 weeks of age, combined with proinsulin tolerance induced at 4 weeks, led to a significant reduction in insulitis that was not observed with either treatment alone. Based on this finding we are working to confirm this result and test the potential for using the combination therapy as a treatment for established autoimmunity.

Supervised by:

  • A/Prof Helen Thomas
  • Dr Bala Krishnamurthy
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Immunology