Antisense oligonucleotide therapies for Amyotrophic Lateral Sclerosis: Existing and emerging targets

•ALS is an incurable and terminal neurodegenerative disease with genetic determinants.•ASOs are targeted molecular therapies.•ASOs can be adapted to target specific genes, downstream targets, or biological pathways in ALS.•ASOs for SOD1- or C9ORF72-linked ALS are currently in clinical trials. Amyotrophic lateral sclerosis (ALS) is a disease with highly heterogenous causes, most of which remain unknown, a multitude of possible disease mechanisms, and no therapy currently available that can halt disease progression. However, recent advances in antisense oligonucleotides have made them a viable option for targeted therapeutics for patients. These molecules offer a method of targeting RNA that is highly specific, adaptable, and does not require viral delivery. Antisense oligonucleotides are therefore being developed for several genetic causes of ALS. Furthermore, biological pathways involved in the pathogenesis of disease also offer tantalizing targets for intervention using antisense oligonucleotides. Here we detail existing and potential targets for antisense oligonucleotides in ALS and briefly examine the requirements for these drugs to reach and be effective in clinic.