Roadmap for developing biologically inspired therapeutics for genetic brain disorders.

A requirement for developing effective therapeutics is to understand the biological events leading to disease. For neuropsychiatric disorders, this will involve understanding how genetic events perturb neural cells and cause circuit dysfunction, impacting behavior. It is now possible to derive human cellular and circuit models of the nervous system to study pathophysiology: organoids to model cell diversity; assembloids to capture cell–cell interactions; transplantation of organoids into behavior-capable circuits. A multilevel approach going from testing cells to probing and manipulating circuits in vivo is emerging as a new way to study disease and offers a glimpse into future therapeutic development.