ABSTRACT
Antisense Oligonucleotide Therapeutics for Neurological Diseases
Antisense oligonucleotides (ASOs) are synthetic, chemical modified nucleic acid analogs designed to bind to RNA by Watson-Crick base paring and upon binding, modulate the function of the targeted RNA. There are a variety of mechanisms by which ASOs can modulate RNA function dependent on the chemical design of the ASO, the type of RNA and where on the RNA the ASO is designed to bind. Both protein coding, as well as non-coding RNAs, can be targets of ASO based drugs, significantly broadening therapeutic targets for drug discovery compared to small molecules and protein-based therapeutics. The recent approval of nusinersen (Spinraza™) as a treatment for spinal muscular atrophy (SMA) and inotersen (Tegsedi) for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) validates the utility of antisense drugs for the treatment of neurological diseases. A summary of the progress, lessons learned and future challenges applying antisense technology for neurological diseases will be provided.