The blood-brain barrier (BBB) plays an essential role in protecting the brain from blood-borne diseases. However, it blocks otherwise effective medicine from reaching the brain. Most drugs developed for treatment of central nervous system diseases fail because they aren’t optimally designed to cross the BBB. There is a need to identify natural transporters acting as ‘shuttles’ that can facilitate the transport of therapeutic cargo attached to their ligand (molecular Trojan horse) into the brain.
By screening thousands of antibodies, the team has isolated several candidates that could efficiently cross the BBB. These human single-domain antibodies were brain selective and modular and could deliver multiple classes of therapeutics, including biologics, across the BBB. Researchers then developed “fusion” molecules consisting of the BBB-crossing antibodies and therapeutic cargo molecules. The efficacy of these “fusion” molecules in treating brain diseases such as brain tumors was tested in preclinical models using novel non-invasive imaging PET scans.
