Device developed in state may help treat brain cancers
Using ultrasound technology and small electric impulses, Connecticut researcher Thanh Nguyen hopes to create doors to the brain, to better allow lifesaving chemotherapy drugs to get where they need to be.
He believes his device could help patients beat some of the most difficult to treat cancers by breaching a person’s natural defense system. There’s a barrier in the brain made up of semipermeable cells. Known as the blood-brain barrier, its job is to keep toxins in the blood from entering the brain.
That natural barrier, as Dr. Alexis Demopoulos, neuro-oncologist and director of neuro-oncology for Hartford HealthCare explained, also makes it more difficult for life-saving medications and therapies to reach the brain.
“The blood-brain barrier makes it challenging to get many medicines into the brain, and in particular it makes it challenging to get many medicines into brain tumors, whether they came from the body or if they grew specifically from the brain itself,” Demopoulos said. “So the blood-brain barrier absolutely is an impediment to our treatments.”
The barrier separates blood vessels from the brain itself, but some things can still get in, Demopoulos said of the circulatory system, adding: “That’s how we get sugar and proteins and oxygen into our brain.”
Large molecules, and
“This research is about making a very new type of ultrasonic transducer, a device that can generate an acoustic wave to facilitate the opening of the blood-brain barrier.”
Thanh Nguyen, Connecticut researcher
even some small ones, can’t pass through the barrier. Most of the time, that’s a good thing. But not always.
“This creates what’s been referred to in the medical literature as a sanctuary space in the brain for cancers,” Demopoulos said. “So, if a cancer can figure out how to survive within the substance of the brain itself, then it gets sort of a golden ticket because a lot of the drugs that we give people that normally destroy the breast cancer, the lung cancer, from the rest of the body, don’t get into the brain or don’t get in enough to be able to wipe out that tumor.”
The blood-brain barrier is so effective that some medications, like the chemotherapy drug paclitaxel, are not often prescribed for brain cancers, despite their known efficacy. But Nguyen says his device could help those lifesaving drugs cross that barrier.
“This research is about making a very new type of ultrasonic transducer, a device that can generate an acoustic wave,” he said, “to facilitate the opening of the bloodbrain barrier.”
Just like a bowed violin string, the device vibrates to create sound, but its vibration is so fast that the sound created is in the ultrasound range, inaudible to the human ear. That ultrasound vibration makes the cells comprising the blood-brain barrier vibrate in concert, which in turn allows medications to pass through to the brain where they are needed.
“The core of this device is a material which they call piezoelectric material and it allows us to control and generate the acoustic wave by applying different voltages, electrical inputs, into this material,” Nguyen said.
The device itself is surgically implanted and triggered electronically when needed, after the chemotherapy drugs are injected. It’s biodegradable, so when it’s no longer needed it simply dissolves after it does its job.
“The brain is a very important organ in the body and so the body wants to create this barrier to prevent toxins and bacteria and viruses from penetrating into the brain when they’re circulating inside the blood vessels,” Nguyen said. “So it’s similar to the drug and that’s why it also prevents it from going into the brain. However, we only open the blood-brain barrier right after we inject the chemo drug into the body.”
According to Demopoulos, there have been a number of strategies used over the years to bypass the blood-brain barrier, as Demopoulos explained: “One of the simplest ways to overcome it is just to give a really big dose of chemotherapy.”
“If only a 10th of the chemotherapy is getting into the brain, you can give 10 times the chemotherapy, and maybe get an effective dose,” he said. “By doing this, we replaced a one-year survival with — some patients are cured and many patients go on to live three, five years or more.”
Doctors have also bypassed the barrier with chemotherapy-laden wafers placed directly on the brain after a tumor has been surgically removed, but Demopoulos said the most exciting attempt is to use the body’s own immune response to kill tumors.
“If you discover somebody with melanoma and brain metastases, who’s never been treated before you can give them these immune stimulating drugs that not only work very well in the body, but if they’re working very well in the body that stimulates the body’s immune system to get into the brain and treat the melanoma there as well,” he said. “So that’s really an exciting opportunity for us to harness the power of the immune system to fight cancers behind that blood-brain barrier.”
Nguyen hopes his device can be another tool in a doctors’ arsenal. It’s only in animal trials at the moment, and Nguyen said he hopes to get approval for tests on human cancer patients within two years.
So far, the device is working exactly as it is supposed to. The animals with which he is working are living longer lives.
“With the ultrasonic device implanted, triggering that opening of the blood-brain barrier, we can see that the tumor was significantly suppressed and the mice live much longer, like two times longer than the control mice,” he said.