Nele Vanderroost

Millions of people worldwide suffer from neurological disorders, including brain tumors. Despite extensive research efforts aimed at finding cures, the treatment options remain largely inadequate. One of the major reasons for the lack of treatment options is the challenge of drug delivery to the brain which requires crossing of the tightly sealed brain barriers, including the blood-cerebrospinal fluid (CSF) barrier at the choroid plexus (ChP). Clearly, there is an urgent need to design novel targeting methods to improve the delivery of therapeutics to the brain (tumor). Single variable domain antibodies or VHHs can be used to target specific receptors at the barriers and consequently exploit the naturally occurring transcytosis mechanisms at the barrier. Recently, the host lab identified a VHH capable of reaching the brain after peripheral injection. To assess the crossing ability of brain targeting VHHs, we currently make use of VHH-neurotensin (NT) peptide fusions. NT induces a measurable hypothermic response upon reaching the hypothalamus. Importantly, this peptide is unable to cross the brain barriers. Consequently, a drop in body temperature after peripheral injections of VHH-NT fusions demonstrates the barrier crossing capacity of the VHH. Recently, we introduced  ChP organoids to replace the in vivo experiments. These ChP organoids are derived from human pluripotent stem cells and produce a CSF-like fluid contained within a functional barrier of choroid plexus epithelial cells. We aim to employ these organoids to screen for barrier crossing VHHs and to unravel the mechanisms by which they do so.
 

• Lab address: Technologiepark-Zwijnaarde 71, 9052 Gent
• Vandenbroucke lab