In this work, we have tested new-generation P2X7 antagonists, the Axxam proprietary compound AXX71 and AXX13, with high selectivity, affinity, and blood brain barrier permeability, for their efficacy on inflammatory/autophagy mechanisms and motor skills in the SOD1-G93A mouse model of ALS. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.