PRKAG3 and proximal spinal muscular atrophy: For metformin, we observed that both 200- and 400-mg/kg/day doses counterintuitively exacerbated Prkag3 downregulation in Smn2B/− SMA muscle instead of the predicted upregulation, which could have negative consequences since Prkag3−/− null mice presented metabolic and mitochondrial dysregulation [94, 95] similar to those reported in SMA patients [46, 74] and models [70, 71].