Disruption of IGF-I/IGFBP interactions decreases contractioninduced injury in dystrophic skeletal muscle

Abstract

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‐31..