Project Summary:
DFMO (difluormethylornithine) is a drug currently in phase II clinical trials for type 1 diabetes (T1D). Armando Puente is building on previous work from his laboratory that studied molecular changes induced by DFMO treatment on mouse models of T1D. His group found that treatment with the drug induced production of a molecule called FGF15 (the human equivalent is called FGF19). The absence of FGF15 in mice causes glucose dysregulation. FGF15 supplementation has been previously shown to have therapeutic effects in mouse models of type 2 diabetes, but it has not been studied in the context of T1D.
Armando’s hypothesis is that one way that DFMO could treat T1D is by increasing levels of FGF15. Therefore, Armando is working to determine the role of FGF15 in the development of T1D and will find out whether it can work as a direct therapy for T1D. He is utilizing an innovative approach of transporting FGF15 mRNA through nanolipid particles directly to the beta cells. This approach will induce FGF15 production by the cells of mice models of T1D.
These experiments will allow Armando to determine if FGF15 can prevent or delay the onset of T1D in the mice. If FGF15 alone can delay or prevent the onset of T1D, this will provide a foundation for further studies on the human form of FGF19 as a potential therapy for T1D.
