Scientists at Oregon Health Sciences University and the Portland Veterans Affairs Medical Center have observed a second barrier that apparently prevents passage of agents from the blood to the brain. The primary barrier is a good thing in a healthy person, but this barrier also keeps drugs such as cancer-fighting chemotherapy from reaching the brain in patients undergoing treatment for brain tumors and other brain malignancies.
Leslie L. Muldoon, Ph.D., assistant professor of neurology, and cell biology and developmental biology, and her colleagues in the Blood-Brain Barrier Program at OHSU report their finding in the February 1999 issue of the American Journal of Neuroradiology (which comes out in March). The group has 20 years of experience with a technique that opens the first blood-brain barrier - an anatomic structure composed of tight junctions in endothelial cells -- to deliver cancer-fighting drugs. But some agents that pass through the first barrier apparently get caught on the second barrier -- called the basement membrane -- and never reach the brain.
The Oregon group is able to get certain therapeutic agents inside the brain with a barrier disruption technique that involves injecting patients with a sugar solution. This solution causes the tight endothelial junctions to shrink and open temporarily. With the barrier down, physicians can get cancer-fighting drugs across the barrier and into the brain - a place drugs don't permeate well with conventional chemotherapy.
More recently, the group has been experimenting on ways to
deliver genes across the blood-brain barrier in rodents. The genes are loaded
onto altered viral vectors, such as the herpesvirus vector or the adenovirus
vector. (Scientists are able to inactivate the dangerous parts of the virus and
then use recombinant techniques to load genes onto the virus. These recombinant
Contact: Henry Sessions or Lee Lewis Husk
Oregon Health & Science University