Repurposed JAK1/JAK2 Inhibitor Reverses Established Autoimmune Insulitis in NOD Mice
Prerak M Trivedi, Kate L Graham, Nicholas A Scott, Misty R Jenkins, Suktilang Majaw, Robyn M Sutherland, Stacey Fynch, Andrew M Lew, Christopher J Burns, Balasubramanian Krishnamurthy, Thomas C Brodnicki, Stuart I Mannering, Thomas W Kay, Helen E Thomas
DIABETES | AMER DIABETES ASSOC | Published : 2017
Recent advances in immunotherapeutics have not yet changed the routine management of autoimmune type 1 diabetes. There is an opportunity to repurpose therapeutics used to treat other diseases to treat type 1 diabetes, especially when there is evidence for overlapping mechanisms. Janus kinase (JAK) 1/JAK2 inhibitors are in development or clinical use for indications including rheumatoid arthritis. There is good evidence for activation of the JAK1/JAK2 and signal transducer and activator of transcription (STAT) 1 pathway in human type 1 diabetes and in mouse models, especially in β-cells. We tested the hypothesis that using these drugs to block the JAK-STAT pathway would prevent autoimmune dia..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by JDRF
Awarded by Government of India, Ministry of Science and Technology, Department of Biotechnology Associateship
This work was funded by the National Health and Medical Research Council (NHMRC) of Australia (grants 1037321, 1061961, 1043414, 1080321, and 1105209), the Leona M. and Harry B. Helmsley Charitable Trust, and JDRF (grants 17-2013-514 and 1-SRA-2016-224); fellowships from the NHMRC (M.R.J., A.M.L., and H.E.T.) and JDRF (B.K. and S.I.M.); and a Government of India, Ministry of Science and Technology, Department of Biotechnology Associateship (BT/20/NE/2011; S.M.). This work also received support from the Operational Infrastructure Support Scheme of the Government of Victoria.