Integrating in vitro disease models of the neurovascular unit into discovery and development of neurotherapeutics.

The blood-brain barrier (BBB) regulates the transport of small molecules, proteins, and cells between the bloodstream and the central nervous system (CNS). Brain microvascular endothelial cells work with other resident brain cell types, including pericytes, astrocytes, neurons, and microglia, to form the neurovascular unit (NVU) and maintain BBB integrity. The restrictive barrier influences the pathogenesis of many CNS diseases, and impedes the delivery of neurotherapeutics into the CNS. In vitro NVU models enable the discovery of complex cell-cell interactions involved in human BBB pathophysiology in diseases including Alzheimer's Disease (AD), Parkinson's Disease (PD) and viral infections of the brain. In vitro NVU models have also been deployed to study the delivery of neurotherapeutics across the BBB, including small molecule drugs, monoclonal antibodies, gene therapy vectors and immune cells. The high scalability, accessibility, and phenotype fidelity of in vitro NVU models can facilitate the discovery and development of effective neurotherapeutics.