Shifting the balance away from canonical and towards noncanonical NF-κB activation is an attractive putative mechanism for the beneficial effects of this antisense therapy in ALS, as p65 NF-κB (which increases with canonical pathway activation), has been strongly implicated in the pathogenesis of ALS through interaction with TDP-43 [22]. Here, NFKB1 is linked to amyotrophic lateral sclerosis.