AbstractIntroduction:Adult muscle fibers are a source of growth factors, including insulin‐like growth factor‐1 (IGF‐1). These factors influence neuronal survival, axonal growth, and maintenance of synaptic connections.Methods:We investigated the components of the IGF system in skeletal muscle samples obtained from 17 sporadic amyotrophic lateral sclerosis patients (sALS) and 29 control subjects (17 with normal muscle and 12 with denervated muscle unrelated to ALS).Results:The muscle expression of IGF‐1 and IGF‐binding proteins 3, 4, and 5 (IGF‐BP3, ‐4, and ‐5, respectively), assessed by immunohistochemistry, was differently decreased in sALS compared with both control groups; conversely, IGF‐1 receptor β subunit (IGF‐1Rβ) was significantly increased. Western blot analysis confirmed the severe reduction of IGF‐1, IGF‐BP3, and ‐BP5 with the increment of IGF‐1Rβ in sALS.Conclusion:In this study we describe the abnormal expression of the IGF‐1 system in skeletal muscle of sALS patients that could participate in motor neuron degeneration and should be taken into account when developing treatments with IGF‐1. Muscle Nerve, 2012