ACCELERATING DRUG REPURPOSING IN PSYCHIATRY USING GENETICS

Abstract

New pharmacotherapies in psychiatry would likely reduce the immense burden that mental health conditions place on individuals and society at large. However, the pipeline to discover novel drugs for use in psychiatric disorders has remained unproductive, where a lack of objective biomarkers for psychiatric diagnoses and the assessment of treatment outcomes contributes to clinical trial failure. Therefore, new approaches are urgently needed to identify more suitable drug candidates for clinical trials. One approach is the integration of human genetic and molecular data to identify and prioritize existing drugs for human clinical trials, known as drug repurposing. This approach has previously been successfully applied in psychiatry and offers an avenue for expedited clinical translation compared to traditional drug discovery. For example, valproic acid was originally used for its anticonvulsant properties in epilepsy before its utility in bipolar disorder was uncovered. Despite the promise of drug repurposing in psychiatry, challenges remain arising from the immense biological heterogeneity of these phenotypes. The advent of well powered, genetic association studies and high throughput measurements on diverse molecular data types (e.g., gene expression) represent an opportunity to better understand the biological complexity of these phenotypes and accelerate successfully translating prospective repurposing candidates into clinical practice. In this symposium, we will outline some of the key methodological considerations and progress to date in genetically informed prioritization of repurposing candidates across psychiatric disorders. Specifically, we will discuss how integration of genetic association signals with multiomic data can reveal prospective opportunities for drug repurposing. Approaches to biologically interpret individual target genes in the context of the wider polygenic architecture of these disorders will also be outlined. Shared genetic liability and biological relationships between psychiatric disorders and somatic disorders across the rest of the body treated by existing drugs additionally can present supporting lines of evidence for prospective repurposing candidates. Finally, given the immense variability observed between individuals with the same diagnosis, we will discuss the prospects of using genetics to target drug repurposing opportunities with greater precision at the individual level. This symposium brings together a diverse set of international researchers that are working at the forefront of innovative approaches to identify opportunities for drug repurposing in psychiatry.