The endocannabinoid system as new target in Duchenn’s muscular dystrophy: getting inside the mechanistic and the anti-inflammatory aspects

The aim the project is to explore, for the first time, the potential of endocannabinoid signaling system (ECS) modulators as co-adjuvant or treatment in Duchenne muscular dystrophy (DMD). We will i) completely characterize ECS in DMD mouse model (mdx); ii) explore the effects of endocannabinoids (EC) and N-acylethanolamines(NAEs) tone modulation; iii) analyze the antioxidant and anti-inflammatory effects associated to this modulation. The recent literature supports a role of the ECS in skeletal muscle differentiation and self-renewal capacity. However, only few studies have been performed demonstrating a) the ability of non-euphoric cannabinoids to promote murine and human satellite cells differentiation via transient receptor potential vanilloid 1 (TRPV1); b) the promotion of myoblast proliferation and inhibition of differentiation to myotubes by cannabinoid receptor 1 (CB1) stimulation, while CB1 antagonists prevent the loss of muscle coordination and strength through a decrease in inflammatory markers. Consequently, a deeper ECS characterization and exploration of its role in skeletal muscle pathophysiology is needed.