VUMC Joins Blood-Brain Barrier Group

Consortium's efforts could improve delivery of chemotherapy to brain tumors

November 12, 2010 | LESLIE HILL

Vanderbilt University Medical Center has joined the International Blood-Brain Barrier Consortium, a group that is combining research and comprehensive patient care to develop protocols and guidelines for opening the blood-brain barrier.

The blood-brain barrier is a system of tight junctions in the circulatory system around the brain that protects the central nervous system from unsafe molecules.

But in some cases, such as targeting a brain tumor with chemotherapy, physicians want certain molecules to cross the blood-brain barrier.

Robert Singer, M.D.

Robert Singer, M.D.

“Chemotherapeutic agents are very big molecules and don’t fit across the gap junctions in the blood-brain barrier,” said Robert Singer, M.D., assistant professor of Neurological Surgery and Radiology and Radiological Sciences.

“But with an infusion of Mannitol, which we use frequently in neurosurgery and trauma when there is brain swelling, we are able to shrink the cells that define the junction, thereby opening the blood-brain barrier.”

Singer is leading VUMC’s participation in the consortium and bringing blood-brain barrier research and therapies to the institution.

“We started a clinical trial to ensure that this was a safe and effective procedure and that outcomes were better,” Singer said. “We found that intra-arterial infusion with blood-brain barrier disruption is 10 times better than intra-arterial infusion alone. We also know there is a four-hour therapeutic window before the barrier closes again.”

The first brain tumor patient was treated with blood-brain barrier disruption in September, and patients are enrolling in five research studies currently under way at the nine medical centers involved in the consortium.

Singer also wants to explore applications of blood-brain barrier disruption in other neurological areas, such as movement disorders, epilepsy and stroke.

For example, tissue plasminogen activator (tPA), the clot-busting drug used to treat acute stroke, kills brain cells and disrupts the blood-brain barrier.

“In neuro-oncology, we’re trying to open up the blood-brain barrier to get chemotherapy agents in. In stroke, we would like to close it down or do something to protect the neurons from tPA,” Singer said.

“Human albumin appears to be one of the best agents in this setting, but you can see how much research there is to be done just in stroke.”

The International Blood-Brain Barrier Consortium was founded by Oregon Health Sciences University. It meets twice a year to discuss best practices and review data from the ongoing multi-center trials.

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