Fig. 4

Chronic pharmacodynamics of GSK978A and NR in MDX hindlimbs following eccentric challenge. a Schematic of chronic study design in MDX and WT mice over 20 weeks (weeks 1-20) showing timing of eccentric contractions (ECC), assessments of contractility (CON), termination and tissue harvest (TERM), and compound administration. GSK978A was dosed daily and contractility was assessed at varying intervals. b Maximal tetanic force production and (c) serum creatine kinase activity assessed at baseline, midpoint, and study conclusion. Arrows indicate timing of eccentric challenges. Significance was determined by repeated measure two-way ANOVA with Tukey’s post hoc test relative to MDX vehicle controls (**p < 0.01, ****p < 0.0001; ns, not significant compared to MDX vehicle controls). d Body composition assessed by qNMR at baseline, week 8, and week 18 of treatment. e Mass and (f) mass ratio of injured and contralateral gastrocnemius muscles collected after 20 weeks of treatment. N = 9-12 mice per group. Mice are MDX unless otherwise noted. Error bars represent SEM. Significance was determined by one-way ANOVA with Tukey’s post hoc test (****p < 0.001, **p < 0.01; ns, not significant)