Abstract

A Translational Neurovascular Model to Study and Identify Therapeutic Targets for Alzheimer’s and Parkinson’s Disease

Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT)

Alzheimer’s Disease and Parkinson’s Disease constitute a current and growing problem for our aging population, and while recent drugs, both FDA-approved and ones at various stages of clinical trial, show promise, nothing is yet available with demonstrated efficacy against either disease.  Most of the current drugs in the pipeline have been developed by traditional methods using high-throughput screens and animal studies, without the benefit of relevant in vitro models of disease.  Several approaches are now being developed, however, with both organ-on-chip and organoid-based models that show considerable potential in recapitulating human neurological disease.  Here we present a model consisting of a microvascular blood-brain barrier with barrier properties comparable to those measured in vivo, consisting of a co-culture of endothelial cells, pericytes and astrocytes.  Extensions to the current model including a neural compartment with healthy neurons and ones modified to express elevated levels of amyloid beta and a meningeal lymphatic system will be presented.  The model is evaluated based on transcriptomic and functional data and demonstrated to be useful for assessing therapeutic delivery across the blood-brain barrier, disease modeling and drug screening.