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Recently, the results of a phase I\/II study using the antisense oligonucleotides Tofersen to treat familial amyotrophic lateral sclerosis with superoxide dismutase 1 mutation have been reported. Intrathecal Tofersen administration resulted in a 36% reduction in superoxide dismutase 1 level in the cerebrospinal fluid. Another report described 2 patients with mutant superoxide dismutase 1 treated with an adeno\u2010associated virus encoding a microRNA targeting superoxide dismutase 1. The first patient, who possessed the fast progressive mutant A5V, received a single intrathecal infusion. Although the patient died of respiratory arrest 16\u00a0months after treatment, autopsy findings showed a reduction of &gt;90% in superoxide dismutase 1 level in the spinal cord. Clinical trials on antisense oligonucleotide therapies targeting other major amyotrophic lateral sclerosis\u2010causative genes, fused in sarcoma and chromosome 9 open reading frame 72, are ongoing. To attenuate the pathology of TDP\u201043, strategies targeting regulators of TDP\u201043 (ataxin 2) and proteins downstream of TDP\u201043 (stathmin 2) by antisense oligonucleotides are being developed. The advent of nucleic acid therapeutics has enabled to specifically attack the molecules in the amyotrophic lateral sclerosis pathological cascade, expanding the options for therapeutic targets. 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