A single low dose of Tb085-SG3376 was able to cure infection in a mouse model of trypanosomiasis.

Three groups of 5 mice were infected with pleomorphic T. b. brucei GVR35-VSL2 cells [32, 33], which allow for parasite burden in live mice to be assessed over a time course by bioluminescent imaging (BLI). BLI was performed prior to any treatment at 3 dpi and then at regular time points following treatment on 3 dpi with a single intravenous dose of (1) 0.25 mg/kg Tb085-SG3376 (n = 5), (2) 0.25 mg/kg NIP228-SG3376 (n = 5) or (3) PBS alone (n = 5). Unlike the control-treated mice, Tb085-SG3376 treatment caused a decrease in the luminescent signal to that obtained from uninfected control animals within 2 days and this remained the case for the duration of the infection, including following the immunosuppression of Tb085-SG3376 treated mice at 66 dpi. Mice treated with NIP228-SG3376 or PBS were culled at a humane endpoint on day 14. (A) Quantification shown is the combined (dorsal + ventral) luminescence over the whole mouse in photons per second (p/s). The corresponding quantification data from the 18 individual mice are shown in S5 Fig. Error bars represent standard deviation. Downward error bars are missing from 4 data points due to scale constraints. (B) For each group of mice selected ventral images for the BLI are shown. Corresponding dorsal images of the same mice are shown in S4 Fig. The scale bar represents the photons emitted at any given point on the image. Exposure times range from 0.5 seconds (for heavily burdened mice) to 5 minutes (for uninfected animals). One mouse in the PBS control group had a lower BLI signal than all other infected mice at 3 dpi (S5 Fig). In the image shown here this mouse appears negative, however, this is due to the low exposure time required for adjacent mice.