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IRBM’s publishes in Cells on establishing a human blood-brain barrier model for use in drug discovery for neurodegenerative diseases such as Huntington’s

IRBM’s publishes in Cells on establishing a human blood-brain barrier model for use in drug discovery for neurodegenerative diseases such as Huntington’s

The blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain. It has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to establish in vitro BBB models. These are valuable tools for studying mechanistic aspects of drug transport to the brain and developing strategic solutions to circumvent the BBB and allow passage of central nervous system (CNS) therapeutics for neurodegenerative diseases such as Huntington’s. This paper describes the establishment of a human BBB model in a two-dimensional monolayer culture, derived from human induced pluripotent stem cells. The model maintained the functionality of major endothelial transporter proteins and receptors. Some proprietary molecules from IRBM’s CNS programs were evaluated revealing comparable permeability in the human model and in the model from primary porcine brain endothelial cells. Given the high attrition rate of CNS drugs in clinical trials, such a model should be valuable for optimizing drug selection and predicting human brain exposure.

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