Breaking through barriers to find a powerful new brain cancer treatment

BY ADRIANA V. DIFRANCO

Hearing Duke neurosurgeon Dr. Gerald Grant talk about his research on the blood-brain barrier (BBB) calls to mind the iconic vault heist scene in Mission Impossible where Tom Cruise is suspended by cables and hovering inches above a pressure-sensitive floor to steal data.

He is attempting to get past a state-of-the-art security system that is sound-sensitive, pressure-sensitive, and even temperature-sensitive.

If you take that security system and multiply it by, say, three orders of magnitude, you start to understand how hard it is for anything to pass through the blood-brain barrier.

“In the past, chemotherapy drugs for brain tumors haven’t been able to get past the blood brain barrier,” says Grant, whose research focuses on using low-frequency ultrasound to open the BBB of patients with brain cancer. “Now we are seeing literal breakthroughs.”

The BBB is a sophisticated, important layer of natural defense that protects the brain. It is designed to keep toxins and pathogens out and allow essential nutrients and oxygen in.

Grant and his team have been studying a safe, minimally invasive approach to better target chemotherapy to treat brain tumors.

The research involves tiny microbubbles given through an IV at the same time as chemotherapy. Once the microbubbles are activated by focused ultrasound, they push against the blood vessels to make space for the chemotherapy to enter the brain. This technique allows the drugs to get past the BBB and release their drug payload deep into the tumor. This approach reduces the overall chemotherapy toxicity, since the method selectively opens the BBB in the area of the tumor.

Duke will soon launch its site for the multi-institutional LIMITLESS trial, to test the safety and efficacy of the technique to treat brain metastases – cancer that has spread to the brain from other parts of the body.

As a pediatric neurosurgeon, Grant knows this method is especially important for children. “If we can open up the blood-brain barrier long enough to get drugs in to shrink a child’s brain tumor, then we may not have to radiate that child’s brain. And that is a huge win,” Grant says. “Irradiating a 5-year old’s brain can have a huge impact on a child’s brain development.”

Speeding up BBB research directly correlates to the collaborative research spirit at Duke within the Preston Robert Tisch Brain Tumor Center, Grant says.

On Duke’s campus, the engineering building is just steps away from the medical school, a proximity that propels new innovation.

“We work very closely with our biomedical engineers in the Pratt School of Engineering, for example, to help target the ultrasound energy during an MRI scan,” he says. “They can better predict precisely what ultrasound power you will need to open the barrier and target the brain tumor.”

Another research advantage Duke has is the ability to deploy a critical “bench-to-bedside” approach, Grant explains.

Duke research scientists can make discoveries in the lab and then quickly take them into clinical trials. If something they try doesn’t work; they can “fail fast” and quickly move on to something else.

That kind of collaboration and innovation means cancer patients can receive effective treatment more quickly.

“Patients can’t wait. It’s too urgent. Tumors are dire. A patient with a malignant brain tumor may die in months,” Grant says. “That’s why patients come to Duke. They know we’re not sitting on anything. The best science we have right now is being applied right now to help that patient today.”

Gerald A. Grant, MD is the Allan H. Friedman Distinguished Professor of Neurosurgery and chair of the Department of Neurosurgery at Duke University’s School of Medicine.