Based on results obtained in vitro which showed that metformin—a widely prescribed drug for type 2 diabetes treatment, known to activate the AMPK pathway [114]—inhibits PKR and reduces the levels of several RAN proteins in mammalian cells, the effect of this drug was tested in vivo by using C9-BAC mice, a C9orf72-based pre-clinical model of ALS [74]. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.