Tideglusib mitigates dystrophic pathology in skeletal muscle and restores diastolic function in young D2 mdx mice

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder that leads to early mortality. We examined the pathogenic contribution of glycogen synthase kinase 3 (GSK3) to DMD using the mdx model. GSK3 is a serine/threonine kinase that has been implicated in other muscular dystrophies and our initial results showed that overactivation of GSK3 may contribute to increased disease severity found in DBA/2J (D2) mdx mice vs C57BL/10 mdx mice. In support of this, treating D2 mdx mice with the GSK3 inhibitor, tideglusib (10 mg/kg/day), increased muscle mass, strength, and fatigue resistance. We also found elevated proportions of oxidative fibers and increased utrophin mRNA, while muscle necrosis and oxidative stress were reduced. Finally, young D2 mdx mice displayed early diastolic dysfunction, and this was blunted with tideglusib treatment – an effect attributed to lowered oxidative stress and fibrosis. This study highlights the therapeutic potential of tideglusib and GSK3 inhibition for DMD. ### Competing Interest Statement The authors have declared no competing interest.