Thus, Leger et al. observed reduced active Akt in skeletal muscle of ALS patients and G93A SOD1 transgenic mice, which may be the “tip of the iceberg.”45 In other words, the reduction of Akt coincides with the decreased expression of IGF-1 and the increased expression of IGF-1R that we observed. Here, SOD1 is linked to amyotrophic lateral sclerosis.