To investigate this alternate hypothesis, we generated constructs containing two mutations, either of the ALS-associated variants, i.e. SARM1V184G or SARM1Δ226–232, together with E642A, a point mutation in the TIR domain that disrupts the catalytic glutamate required for SARM1 NAD+ hydrolase activity and axon degeneration [23, 41–44]. The gene discussed is SARM1; the disease is amyotrophic lateral sclerosis.