ReviewKeynoteEmerging RNA editing biomarkers will foster drug development

•Attrition of candidate drugs because of adverse CNS reactions remains a major concern.•RNA editing fine-tunes neural function at the synaptic level.•Drug-associated alterations of RNA editing was shown in neuropsychiatric disorders.•Assessment of RNA editing profiles will foster drug development.

Unanticipated adverse drug reactions (ADRs) on the central nervous system are a major cause of clinical attrition and market withdrawal. Current practices for their prospective assessment still lean on extensive analysis of rodent behaviour despite their highly controversial predictive value. Human-derived in vitro models that objectively quantify mechanism-related biomarkers can greatly contribute to better ADR prediction at early developmental stages. Adenosine-to-inosine RNA editing constitutes a physiological cellular process that translates environmental cues by regulating protein function at the synaptic level in health and disease. Robust solutions based on NGS-based quantification of RNA editing biomarkers have emerged to predict the likelihood of treatment-related suicidal ideation and behaviour allowing cost-effective high-throughput drug screening as a strategy for risk mitigation.