Antibody disrupts blood-brain barrier

Cells along the blood vessels in the brain form tight junctions to prevent toxic molecules—and often drug molecules—from entering the brain. Researchers have found an antibody that disrupts this blood-brain barrier in some people with an autoimmune disease (Sci. Transl. Med. 2017, DOI: 10.1126/scitranslmed.aai9111). The findings could lead to strategies to deliver drugs to the brain, the researchers say. Neuromyelitis optica is an autoimmune disease in which the immune system attacks a certain protein in brain cells, often leading to inflammation and damage to the optic nerve and spinal cord. Antibodies targeting this protein can get past the blood-brain barrier, so scientists wondered how they performed the feat. A team led by Richard M. Ransohoff of Biogen and Jeffrey L. Bennett of the University of Colorado School of Medicine found that another antibody in patients’ blood can bind to and activate the endothelial cells responsible for forming the barrier. The team determined that this antibody targeted glucose-regulated protein 78 (GRP78) on the cells’ surfaces. Injecting the GRP78 antibody into mice daily for seven days increased the permeability of the animals’ blood-brain barriers, allowing proteins of different sizes to leak into the brain from the blood. Disrupting the blood-brain barrier for drug delivery is fraught with neurotoxicity issues, says William A. Banks of the University of Washington and VA Puget Sound Health Care System. But, he says, this study’s findings give scientists a new player to study to better understand the regulation of this important interface between the blood and brain.