Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases

The rising median age of our population and the age-dependent risk of neurodegeneration translate to exponentially increasing numbers of afflicted individuals in the coming years. Although symptomatic treatments are available for some neurodegenerative diseases, most are only moderately efficacious and are often associated with significant side effects. The development of small molecule, disease-modifying drugs has been hindered by complex pathogenesis and a failure to clearly define the rate-limiting steps in disease progression. An alternative approach is to directly target the mutant gene product or a defined causative protein. Antisense oligonucleotides (ASOs) – with their diverse functionality, high target specificity, and relative ease of central nervous system (CNS) delivery – are uniquely positioned as potential therapies for neurological diseases. Here we review the development of ASOs for the treatment of inherited neurodegenerative diseases.