Disruption of IGF-I/IGFBP interactions decreases contraction-induced injury in dystrophic skeletal muscle.

Duchenne muscular dystrophy (DMD) is caused by a lack of dystrophin, a structural protein thought to confer stability to skeletal muscle fibers. A lack of dystrophin results in an increased susceptibility to contraction-induced (CI) injury. Insulin-like growth factor-I (IGF-I) therapy has beneficial effects on muscle function in mdx mice, a model of DMD. The actions of IGF-I are strongly modified by IGF binding proteins (IGFBPs). The IGF-I aptamer, NBI-31772, displaces IGFBPs from their interaction with IGF-I, releasing free biologically active IGF-I. We tested the hypothesis that disruption of IGF-I/IGFBP interactions using NBI-31772 would reduce the dystrophic pathology in mdx mice. NBI-31772 was administered to mdx mice (continuous infusion; ∼6 mg/kg/day) for 4 weeks via mini osmotic pump. Muscle contractile properties were examined in vitro. NBI-31772 treatment reduced the susceptibility of the EDL and diaphragm muscles to CI injury, concomitant with reduced fatigue resistance and lower citrate synthase activity. The findings indicate that displacing IGF-I from its binding proteins can protect dystrophic muscles from CI injury. [ABSTRACT FROM AUTHOR]