New Treatment for Glioblastoma: Ultrasound Opens Blood-Brain Barrier for Highly Effective Chemotherapy Drugs

A major obstacle in the treatment of Glioblastomen was that the most effective drugs used in chemotherapy do not reach the aggressive brain tumor because they cannot penetrate the blood-brain barrier. This highly effective filter between the fluid spaces of the bloodstream and the central nervous system protects the brain from pathogens and toxins, but also shields it from the vast majority of drugs.

Patients with brain tumors can therefore not be treated with most drugs that are effective in other types of cancer. According to the study, which is now in the specialist journal “The Lancet Oncology” published, enable a four- to six-fold increase in drug concentration in the brain.

Process takes four minutes

To open the blood-brain barrier and administer the chemotherapy, the scientists at Northwestern University in the US used a grid of nine ultrasound transmitters that could be implanted in the skull, developed by the French biotech company Carthera was developed. This allows large regions of the brain to be penetrated repeatedly, temporarily increasing the permeability of the blood-brain barrier. The drug for chemotherapy is administered intravenously beforehand and can penetrate the area of ​​the tumor through the sonication.

The process takes four minutes, the patients are awake and can go home after a few hours. The results show according to the research team around the neurosurgeon Adam Sonbendthat the treatment is safe and well tolerated.

Use of highly effective drugs possible

So far I give it Temozolomid only a drug for chemotherapy for glioblastomas, although this crosses the blood-brain barrier, it is “a weak drug”, according to Sonabend in a broadcast. The increase in drug concentration in the brain by a factor of four to six could be observed with two highly effective drugs: Paclitaxel and Carboplatin.

These two drugs have not been used to treat glioblastoma because, under normal circumstances, they cannot cross the blood-brain barrier. In previous studies, paclitaxel was injected directly into the human brain, but a connection with meningitis was observed here.

According to the neurosurgeon, the clinical study could represent a major step forward for glioblastoma patients. What’s more: “Although we have focused on brain tumors, the method opens the door to research into new treatments for millions of patients suffering from various brain diseases.”

The barrier closes again after an hour

The research results form the basis for a Phase 2 clinical trial ongoing, which Sonabend’s research team is currently carrying out: With the new procedure, the patients receive a combination of paclitaxel and carboplatin. The aim of the study is to investigate whether this treatment prolongs people’s lives.

In the study, the researchers also describe how quickly the blood-brain barrier closes again after the ultrasound. Most of the recovery of the blood-brain barrier therefore takes place in the first 30 to 60 minutes after the ultrasound. “There is a critical time window after sonication in which the brain is permeable to drugs that circulate in the bloodstream,” says Sonabend. This finding should make it possible to optimize the timing of drug delivery and activation of the ultrasound.