Senior Scientist Takeda Development Center Americas, Inc. Cambridge, Massachusetts
Neurological conditions are the leading cause of illness, but over 92% of clinically tested CNS drug candidates fail to become treatments. Contributing to this high failure rate is a lack of understanding of human disease mechanisms, technologies to address them, and the restrictive blood-brain barrier (BBB), which most compounds fail to cross. New models are critically needed that more faithfully recapitulate human neurological disease. Recently, we have developed a multicellular human Brain-on-Chip, combining iPSC-derived cells of each of the six major brain cell types into an engineered 3D tissue utilizing a brain-mimicking biomaterial scaffold and novel microfluidic platform. Brain-on-Chips form 3D immuno-glial-neurovascular units with enhanced cell- and tissue-scale phenotypes inclusive of myelinated neuronal networks, microglial immune cells, and perfusable BBB. This technology provides potential advantages at each step in preclinical drug development: a tool for discovery of biomarkers and targets, evaluation of therapeutic efficacy and delivery, and personalized drug screening.
Learning Objectives:
define bottlenecks in neurological disease drug discovery and development pipeline.
describe key components of brain pathologies critical to drug development.
define bottlenecks in neurological disease drug delivery.
describe key cellular barriers governing drug delivery to the brain.
discuss Human Brain-on-Chip with advantages for preclinical development.
