The blood-brain barrier acts as a partial barrier to toxic substances and microorganisms
Carol &; Mike Warner/Science Photo Library
Ultrasound can help open the blood-brain barrier, allowing more targeted treatment of hard-to-reach brain tumors.
The blood-brain barrier (BBB) is made up of many cell types that help protect organs from toxic substances and microbes that may be circulating in the bloodstream. It can also prevent agents from reaching malignant cells.
Now, Adam Sonabend of Northwestern University, Illinois, and colleagues used low-intensity pulsed ultrasound to open the BBB in 17 people with recurrent glioblastoma multiforme (GBM), an advanced brain tumor. . Existing treatments focus on removing as much of the tumor as possible, followed by radiation therapy and the chemotherapy drug temozolomide. Temozolomide can cross his BBB, but weakly compared to other cancer drugs.
Seventeen participants underwent a craniotomy, an operation in which the head was opened to expose the brain and part of the tumor was removed. In this surgery, a so-called SonoCloud-9 (SC9) device that emits ultrasound waves was placed in a cutout area of the skull.
Some participants received the chemotherapy drug paclitaxel during the surgery, and its levels were measured in the brain.
After 1–3 weeks, all of the participants’ SC9 devices were activated via the pulse generator. During this activation, doctors injected microbubbles into the participants’ brains. These moved in response to ultrasound, creating mechanical stress that helped open the BBB.
This procedure took 4 minutes and participants remained awake the entire time. Thereafter, paclitaxel was administered intravenously to him, increasing the dose every 3 weeks for up to 6 cycles.
After the intervention, participants’ mean brain concentrations of paclitaxel were 3.7-fold higher than when the drug was administered without the SC9 device activated during the early stages of the experiment. It’s unclear if this improves survival for patients with recurrent GBM, but higher drug concentrations in the brain suggest more effective treatment outcomes, the researchers said.
Participants’ BBBs closed within an hour and were able to perform normal functions.
Sonabend says that repeated opening and closing of the BBB over many cycles of the intervention did not produce any appreciable side effects. Headache was the most commonly reported adverse event, affecting 71% of participants. Pins and needles, facial or limb weakness, and blurred vision have also been reported, but these were all temporary.
“This study shows that the procedure is feasible and safe for humans,” said Michael Lim of Stanford University in California. It can be very helpful for patients with blastoma.”
The BBB can already be opened by some drugs, but the procedure could open a larger portion of the barrier, allowing more anticancer drugs to penetrate, Lim says.
The researchers are now giving paclitaxel along with another chemotherapy drug, carboplatin, and are testing this approach in more GBM patients when the two treatments are given together. Sonabend said.
