Understanding the Blood-Brain Barrier (BBB) and Its Role in CNS Drug Development

The blood-brain barrier (BBB) plays a crucial role in maintaining homeostasis between the cerebral vasculature and the brain. It tightly regulates the influx and efflux of substances, both in healthy and diseased states, making it a key target in CNS drug development.

Advancing BBB Models with Stem Cell Technology

Recent advancements in stem cell technology have enabled the use of human brain-specific cells to establish in vitro BBB models. These models are essential tools for studying the mechanistic aspects of drug transport to the brain. They also provide strategic solutions for overcoming the BBB and facilitating the delivery of central nervous system (CNS) therapeutics, especially for neurodegenerative diseases like Huntington’s.

Establishing a Human BBB Model

In this study, we developed a human BBB model using a two-dimensional monolayer culture derived from human induced pluripotent stem cells (iPSCs). The model successfully retained the functionality of key endothelial transporter proteins and receptors, crucial for accurately mimicking human BBB conditions.

Evaluating CNS Drug Permeability in Human and Porcine Models

To validate the model, proprietary molecules from IRBM’s CNS programs were tested. The results showed comparable permeability in the human model and a model derived from primary porcine brain endothelial cells, highlighting the reliability of our human-based BBB model.

Improving Drug Selection for CNS Therapeutics

Given the high attrition rate of CNS drugs in clinical trials, utilizing a robust and predictive BBB model is critical. Our model offers a valuable tool for optimizing drug selection and accurately predicting human brain exposure, which is key for advancing CNS therapeutics from research to clinical application.