BREAKING THROUGH THE BBB: Some researchers are engineering bispecific antibodies (yellow and green molecules), with one arm serving to help the molecule cross the blood-brain barrier (BBB) while the other arm dictates the drug’s function in the brain.COURTESY OF RYAN WATTS/GENENTECH. FROM SCIENCE TRANSLATIONAL MEDICINE VOL 3, ISSUE 84 (25 MAY 2011). REPRINTED WITH PERMISSION FROM AAAS.When neuroscientist Ryan Watts talks about receptor-mediated transcytosis, he sounds like an orchestra conductor describing his favorite piece of music. To him, the passage of a molecule through a cell membrane via a receptor-assisted vesicle is an art form, and, more importantly, a way into the brain.
In 2004, Watts formed the neuroscience unit at pharmaceutical company Genentech. Right away, he organized a program to develop antibodies against the protein fragment amyloid beta, a component of brain plaques associated with Alzheimer’s disease. But as soon as he began, Watts, like many before him, ran into a wall—literally. His antibodies were being trapped at the blood-brain barrier (BBB), a mesh of tight junctions between specialized endothelial cells lining brain capillaries that prevent foreign particles from entering the brain.
Antibodies actually can get into the brain, just not very efficiently. For every thousand antibodies injected into the blood, only one will find its way into the brain, likely by slipping unnoticed into vesicles crossing the barrier. Unfortunately, that dramatic concentration decrease prevents researchers from ...
