Ongoing | January 2023 - December 2026

Establishment and validation of a human in vitro model to investigate uptake transport at the Blood-Brain Barrier

DP-2022-001

The Blood-Brain Barrier is a structure between the central nervous system (CNS) and the bloodstream, whose main role is to protect the CNS from toxic compounds while allowing the passage of nutrients. Importantly, due to the activity of drug efflux transporters the Blood-Brain Barrier is seen as an obstacle for brain targeting drugs. This mechanistic understanding mostly relies on data from rodents, as it is difficult to measure and collect data on drug accumulation in the brain in humans. However, transferability of rodent data to the human system is violated by the fact that there are discrepancies in expression levels, substrate specificity, and number of isoforms. Yet, it is widely accepted that there are drug transporters facilitating cellular uptake in endothelial cells of the Blood-Brain Barrier. In order to investigate and understand their contribution to the net transcellular transport at the Blood-Brain Barrier we are aiming to establish and validate a human in vitro Blood-Brain Barrier model applicable to study uptake transporters, more specifically the Organic Anion Transporting Polypeptide (OATP)1A2 and OATP2B1. After establishment and validation we will apply the model to assess their impact on the transcellular transport of drugs and endogenous molecules, including neurosteroids. The establishment of such a human in vitro model to study transport at the Blood-Brain Barrier will contribute to the replacement of animal models and will help to reduce the use of animals in science.

https://swiss3rcc.org/media/pages/funded-projects/2022-doctorate-programme-establishment-and-validation-of-a-human-in-vitro-model-to-investigate-uptake-transport-at-the-blood-bra/412add4dcb-1682594750/valerio-taggi.jpg

Valerio Taggi, Universit├Ąt Basel