Antisense Oligonucleotide Based Therapies for Neurological Diseases
C. Frank Bennett Ionis Pharmaceuticals., Carlsbad, USA
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. These include promoting the degradation of the target RNA and modifying intermediate metabolism such as splicing or polyadenylation. 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 as a treatment for spinal muscular atrophy (SMA) validates the utility of antisense drugs for the treatment of motor neuron disease. A brief overview of the nusinersen program will be presented to highlight the utility of antisense technology for neurological diseases. Progress in developing antisense drugs for other neurological diseases, including Huntington's disease will be discussed.