Antisense oligonucleotides on neurobehavior, respiratory, and cardiovascular function, and hERG channel current studies

The absence of direct actions on neurobehavior and respiratory function associated with the administration of ASOs in safety pharmacology core battery studies is consistent with published toxicology studies. The combination of in vitro hERG studies and in vivo studies in rat and monkey are consistent with no direct actions by ASOs on cardiac cell function or electrical conduction at relevant concentrations and dose levels. Taken as a whole, dedicated studies focused on the safety pharmacology of specific organ systems do not appear to add significant data for interpretation of potential adverse effects. The need for dedicated studies for future ASOs in the same class is questionable, as a more encompassing data set can be collected in repeat dose and longer-term toxicology studies.