Clinical trials for other common targets in macrophage signaling pathways, such as TNF‐α, IL‐6, IL‐1, PI3K/Akt, and sphingosine 1‐phosphate receptor (S1PR), are being conducted in ALS patients, among which the S1PR agonist fingolimod, IL‐6R antagonist tocilizumab, and IL‐1R antagonist anakinra demonstrate good safety and tolerability,250, 251, 252 and a modulator of the PI3K/Akt pathway RNS60 shows a positive effect,253 whereas the trial of the TNF‐α antagonist thalidomide has failed.254. This evidence concerns the gene TNF and amyotrophic lateral sclerosis.