Methods: Human pluripotent stem cells (HiPSC) were differentiated to cardiomyocytes (HiPSC-CM). Vero cells or HiPSC-CM were infected with the Trypanosoma cruzi trypomastigotes Y strain in the presence of itraconazole and/or amiodarone. After 48 hours, infection and multiplication were evaluated by Giemsa stain. Benznidazole was used as a reference compound. Cell viability was verified by XTT assay.
Results: Itraconazole and amiodarone showed dose-dependent interference with Trypanosoma cruzi infection of Vero cells or HiPSC-CM. The combination of itraconazole and amiodarone was more potent than the single substances, or benznidazole at therapeutic concentrations, without affecting host cell metabolism. In addition to effects on infection, itraconazole, or amiodarone affected Trypanosoma cruzi multiplication. Here, itraconazole / amiodarone combinations were more potent than either alone, both, in Vero cells, and HiPSC-CM.
Conclusion: Our in vitro data suggest that a combination of itraconazole and amiodarone might serve as an effective new treatment option for Chagas disease, particularly cardiac involvement, in human and animal patients.
A. Bozzi, None
N. Sayed, None
J. Wu, None
D. Stevens, None