The druggable schizophrenia genome: from repurposing opportunities to unexplored drug targets
Santiago G. Lago, Sabine Bahn
Abstract
There have been no new drugs for the treatment of schizophrenia in several decades and treatment resistance represents a major unmet clinical need. The drugs that exist are based on serendipitous clinical observations rather than an evidence-based understanding of disease pathophysiology. In the present review, we address these bottlenecks by integrating common, rare, and expression-related schizophrenia risk genes with knowledge of the druggability of the human genome as a whole. We highlight novel drug repurposing opportunities, clinical trial candidates which are supported by genetic evidence, and unexplored therapeutic opportunities in the lesser-known regions of the schizophrenia genome. By identifying translational gaps and opportunities across the schizophrenia disease space, we discuss a framework for translating increasingly well-powered genetic association studies into personalized treatments for schizophrenia and initiating the vital task of characterizing clinically relevant drug targets in underexplored regions of the human genome.