AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy

Adiponectin (ApN) is a hormone known to possess powerful anti inflammatory and pro myogenic effects on skeletal muscle. Duchenne muscular dystrophy (DMD) is a devastating disease characterized by dystrophin deficiency with subsequent chronic inflammation, myofiber necrosis and impaired regeneration. Previously, we showed that transgenic upregulation of ApN could significantly attenuate the dystrophic phenotype in mdx mice (model of DMD). AdipoRon is a synthetic small-molecule ApN receptor agonist that has the advantage of being more easily produced and administrable than ApN. The aim of this study was to investigate the potential effects of AdipoRon on the dystrophic muscle. Two months treatment with AdipoRon (mdx-AR mice) strongly mitigated oxidative stress and inflammation (- 35-65% for all markers, p<0.0001 vs. untreated mdx) while increasing the anti-inflammatory cytokine, IL-10 (5-fold, p<0.0001). AdipoRon also improved the myogenic program as assessed by a 2-fold rise in markers of muscle proliferation and differentiation, p<0.01). Plasma LDH and CK were reduced by 30-40% in mdx-AR mice, reflecting less sarcolemmal damage (p