Microphysiological models of neurological disorders for drug development

Abstract Clinical trials of drug candidates intended to treat neurological conditions often fail due to the poor correlation between outcomes in humans and other animal models. Microphysiological systems offer a potential alternative to, or synergetic approach with animal testing by using human cells assembled in three-dimensional morphologies that are representative of human tissues and organs. The recent advances in microphysiological models of neurological disorders are reviewed here in terms of models used to quantify drug distribution and drug engagement and function. We find that the complexity of MPS models continues to increase, but only few neurological conditions have been modeled with the purpose of testing pharmacological traits of candidate drugs. Much more effort appears to have been devoted to models that recapitulate drug distribution, particularly across vascular barriers, and models involving barrier modifications as a result of patient-specific neurological conditions have started to emerge. Based on the current trend, microphysiological models of neurological disorders have the capacity to become a useful tool in the pre-clinical testing of drugs for human use.