French scientists have carried out the first human trial of an ultrasound device that pushes drugs through the “blood-brain barrier”, potentially clearing a big obstacle to using chemotherapy on brain tumours.
The barrier, a protective layer of cells around cerebral blood vessels that shields the brain from toxins, makes neurological disease, and tumours in particular, notoriously hard to treat.
Patients either have to take drugs in huge quantities so that some molecules get through the barrier from the bloodstream, or drugs have to be delivered by other means such as a direct injection into the brain.
During the trial, however, ultrasound pulses enabled patients with incurable brain tumours to receive chemotherapy that otherwise would not have reached their cancer cells.
“The blood-brain barrier is one of the last major frontiers of neuroscience,” said Alexandre Carpentier, neuroscience professor at Pitié-Salpêtrière Hospital in Paris, who led the project team with researchers from several French institutions. “We can make the blood vessels temporarily permeable, so that chemotherapy molecules can penetrate the brain.”
Prof Carpentier and his colleagues have developed SonoCloud, an ultrasound device that is 11mm in diameter. A surgeon can install the device in a patient’s skull either at the end of an operation to remove a brain tumour or after taking a biopsy.
The clinical trial involved 15 patients with glioblastoma, a particularly aggressive brain tumour, who were fitted with SonoCloud and received carboplatin, an established chemotherapy drug.
Preliminary results, published in the journal Science Translational Medicine, show the treatment is safe, well tolerated and delivers carboplatin to the brain. Some patients responded well but it is too soon to assess the treatment’s efficacy.
SonoCloud is activated every month for a patient’s chemotherapy session, first by injecting microscopic bubbles of perfluorocarbon (PFC) into the bloodstream and then connecting the device to an external power source. This beams ultrasound into the brain for two minutes.
The ultrasound makes the bubbles vibrate inside the brain’s blood vessels, temporarily stressing their protective outer layer and making them permeable for about six hours. During this period the patient receives an intravenous infusion of carboplatin, which leaks through the cerebral blood vessels into the cancerous area of the brain.
“We can carry out this procedure every month for six months if necessary,” said Prof Carpentier. It has no long-term effect on the blood vessels or on healthy neurons, he added.
A private spinout company called CarThera has been set up to commercialise the ultrasound technology. “We plan to raise money in 2017 to fund a large-scale clinical trial of 200 patients with centres in Europe and the US,” said Frédéric Sottilini, CarThera chief executive. “SonoCloud could be commercially available in 2020 for use in recurrent glioblastoma.”
The company estimates that, of the 250,000 patients worldwide who are diagnosed with a brain tumour every year, 160,000 could benefit from SonoCloud treatment — creating a market worth $1.7bn annually.
Prof Carpentier and colleagues believe the technology could have applications beyond brain cancer, including treating Alzheimer’s disease.
Animal tests have shown that opening the blood-brain barrier with ultrasound pulses can prompt the immune system to attack the amyloid plaques that accumulate in Alzheimer’s. Clinical trials to discover whether this will help human patients could begin next year.