Ultrasound opens brain barrier so drugs can reach aggressive tumors

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The blood-brain barrier acts as a barrier against toxins and microorganisms

Carol & Mike Werner / Science Photo Library

Ultrasound waves help open the blood-brain barrier, which may allow more targeted treatment of hard-to-reach brain tumors.

The blood-brain barrier (BBB) ​​is made up of several types of cells that help shield the brain from toxins and microorganisms that may circulate in the bloodstream. However, this roadblock may also prevent cancer drugs from reaching malignant cells in the brain.

Now, adam sonnabend at Northwestern University, Illinois, and colleagues used low-intensity pulsed ultrasound to open the BBB of 17 people with recurrent glioblastoma multiforme (GBM), an aggressive brain tumor. Current treatments focus on removing as much of the tumor as possible, followed by radiotherapy and the use of the chemotherapy drug temozolomide, which can cross the BBB, but is weaker than some other anti-cancer drugs.

The participants underwent a craniotomy, an operation to open the head to expose the brain, which enabled doctors to partially remove their tumors. During this surgery, a Sonocloud-9 device, which emits ultrasound waves, was implanted in the cutout area of ​​his skull.

Some participants received the chemotherapy drug paclitaxel during this surgery and its concentration was measured in their brains.

Between weeks one and three, all of the participants’ ultrasound devices were activated. During this activation, micro-bubbles were injected into the brains of the participants. The bubbles moved in response to the ultrasound waves, creating a mechanical tension that helped open the BBB.

The procedure took 4 min and participants remained awake throughout. Paclitaxel was then given intravenously at increasing doses every three weeks for six cycles.

After the intervention, the mean concentration of paclitaxel in the brain was 3.7 times higher than when the drug was given without the ultrasound equipment activated earlier in the experiment. The researchers say it is unclear whether this improves survival among people with recurrent GBM, but a higher drug concentration in the brain suggests more effective treatment outcomes.

They say that the BBB closed within 1 hour, enabling it to perform its regular functions.

Repeated opening and closing of the barrier over several cycles of the intervention did not cause any serious side effects, Sonnabend says. Headache was the most common adverse event, affecting 71 percent of participants. Some also reported pins and needles, weakness of the face or limbs, and blurred vision, all of which were temporary.

Study shows this procedure is feasible and safe in people, says Michael Lim at Stanford University, California. “A small, implantable device that can open the BBB in an outpatient clinic could be of great help to glioblastoma patients.”

The BBB can already be opened with some drugs, Lim says, but this process can open a larger section, allowing more of the cancer drug.

Researchers are now testing the approach in more people with GBM when paclitaxel is administered with the chemotherapy drug carboplatin, which is usually given together, says Sonnabend.

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