RNA therapeutics for mood disorders: current evidence towards clinical trials

Abstract

Introduction Mood disorders are severe yet frequent psychiatric disorders worldwide, comprising major depressive disorder (MDD) and bipolar disorders (BD). Their treatment remains poorly effective. For the past decades, various pathophysiological processes have been explored and growing evidence for epigenetic mechanisms has emerged. Consequently, a great interest in a novel pharmacological class for the treatment of mood disorders arose: RNA therapeutics. Areas covered We conducted a systematic review of RNA therapeutics ─ antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs) and micro-RNA (miRNA) therapeutics ─ for the treatment of mood disorders studied in pre-clinical animal models listed in PubMED, in clinical trials registered in ClinicalTrials.gov and available on the market by combining literature search and Food and Drug Administration (FDA) and European Medicine Agency (EMA) online databases. Eighteen pre-clinical studies investigated the antidepressant effects of RNA therapeutics. However, even though there is an increasing number of marketing authorizations and clinical trials for the past twenty years, no RNA therapeutic reached the clinical development pipeline for the treatment of psychiatric disorders yet. Expert opinion Several promising RNA therapeutics have been tested in pre-clinical studies for depressive disorders, whereas no molecule has been developed for BD. There are several issues to address before reaching clinical development and new challenges include stratifying patient population and predicting therapeutic response.