Over the past few years, ArmaGen Technologies Inc. and collaborators at the University of California, Los Angeles, have published a series of studies describing genetically engineered fusion proteins to shuttle therapeutics across the blood-brain barrier. In their newest paper in Molecular Pharmaceutics, the group presented in vitro data on AGT-185, a chemical nerve gas antidote created using the company's technology platform.1
ArmaGen's approach takes a therapeutic that would not ordinarily cross the blood-brain barrier (BBB) and links it to a BBB-targeting mAb. The resulting fusion protein enters the CNS via a receptor-mediated molecular transport system in the vascular endothelial cells that make up the BBB (see "Breaching the blood-brain barrier").
The study in Molecular Pharmaceutics focused on paraoxonase 1 (PON1), a serum esterase that inactivates organophosphate toxicity caused by exposure to pesticides and nerve gas agents.
Naturally occurring PON1 cannot cross the BBB. In this case, the researchers linked it to a mAb targeting the