Figure 6.

GTx-026 improves the lung function in mdx mice. (A) GTx-026 alters heart and respiratory rates (RRs) and increases blood oxygen levels. Wild-type or mdx mice (n = 4–5/group) were castrated and treated with vehicle or 10 mg/kg/day s.c. GTx-026 for 10 weeks. At the end of the experiment, RR, heart rate (HR) and oxygen content (SPO₂) were measured using STARR Life Sciences “MouseOx” with 6.2.1 software version. All recordings were taken over 2–3 minutes with the highest SPO₂% recorded for each mouse and the corresponding HR and RR at that particular SPO₂% value. (B) Energy expenditure and activity of mice were improved by GTx-026. Wild-type or mdx mice (n = 4–5/group) were either sham operated or castrated and treated with vehicle or 10 mg/kg/day s.c. GTx-026 for 10 weeks. At the end of the experiment, the mice were maintained in Comprehensive Laboratory Activity Monitoring System (CLAMS) for 48 h. Oxygen consumption and activity were measured continuously for 48 h. Averages are provided in the top panels and the continuous measurements are provided in the lower panel. Dark phase is the night time when mice are active. *Significance at P < 0.01 from the respective controls. (C) Lung function is significantly improved by GTx-026 in mdx mice. Wild-type or mdx mice were castrated and treated with vehicle or 10 mg/kg/day s.c. GTx-026 for 12 weeks. Airway resistance to methacholine challenge (MeCh; Sigma-Aldrich) was measured using the FlexiVent FX system (Scireq, Montreal, QC, Canada). Raw data were fitted into a single—compartment model and resistance data were calculated. When no significant difference was observed in baseline values at 0 mg/ml MeCh among groups, airway resistance was normalized and presented as normalized resistance [(values – baseline)/baseline×100%]. N = 4–5/group. Data are represented as average ± SE. *Significance at P < 0.05. (D) Mason trichrome staining for collagen indicates reduced fibrosis in lungs from GTx-026-treated mice. Lungs from animals used in the flexivent study were fixed and stained with mason trichrome stain for collagen as a measure of fibrosis. Stains were scored between 0 and 3 based on the intensity of stain. % SPO₂, % of hemoglobin oxygenated; VO₂, volume of oxygen; MeCh, methacholine.