First, since a major hallmark of ALS is progressive muscle atrophy [33], FGF21 would be expected to increase over time because of its correlation with atrophied myofibers (Figure 2) and HDAC4 (Supplementary Figure 1), a muscle biomarker that associates with progressive muscle denervation in ALS [31]. This evidence concerns the gene HDAC4 and amyotrophic lateral sclerosis.