Ultrasound opens brain barrier so drugs can reach aggressive tumours

Ultrasound waves help to open up the blood brain barrier, which could allow for more targeted treatment of hard-to-reach brain tumours.

The blood brain barrier (BBB) is made up of many cell types that help to shield the organ from toxic substances and microorganisms that may be circulating in the bloodstream, but this roadblock can also prevent cancer drugs from reaching malignant cells.

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

The 17 participants underwent a craniotomy, an operation to open the head to expose the brain, to remove part of their tumours. During this surgery, a so-called SonoCloud-9 (SC9) device, which emits ultrasound waves, was fitted into a cut out region of their skulls.

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

Between 1 and 3 weeks later, all of the participants’ SC9 devices were activated via a pulse generator. During this activation, the doctors administered microbubbles into the participants’ brains. These moved in response to the ultrasound waves, creating a mechanical stress that helped to open the BBB.

The procedure took 4 minutes and the participants remained awake throughout. Paclitaxel was then administered intravenously at an increasing dose every 3 weeks for up to 6 cycles.

After the intervention, the participants’ average brain concentration of paclitaxel was 3.7 times higher than when the drug was administered without the SC9 devices being active earlier in the experiment. 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, say the researchers.

The participants’ BBB closed within 1 hour, enabling it to perform its regular functions, they say.

The repeated opening and closing of the BBB over the intervention’s numerous cycles didn’t cause any apparent side effects, says Sonabend. Headache was the most commonly reported adverse event, affecting 71 per cent of the participants. Some also reported pins and needles, facial or limb weakness, and blurred vision, all of which were temporary.

The study has shown this procedure is feasible and safe in people, says Michael Lim at Stanford University, California. “A small, implantable device that can open up the BBB in outpatient clinic can be very helpful for glioblastoma patients.”

The BBB can already be opened with some medications, but this procedure could open a larger section of the barrier, allowing more of a cancer drug to penetrate, says Lim.

The researchers are now testing the approach in more people with GBM when paclitaxel is administered alongside the other chemotherapy drug carboplatin, with these two treatments often being given together, says Sonabend.