The blood-brain barrier is an almost impenetrable membrane that surrounds vessels in the brain and stops harmful particles from entering. The trouble is that it doesn't discriminate, at the same time making it very difficult for beneficial molecules like medication to pass through. But researchers have now non-invasively breached the barrier for the first time in a human subject, delivering chemotherapy drugs to a brain cancer patient with a high level of precision and paving the way for improved treatments and fewer side effects for sufferers of neurological disorders.
The blood-brain barrier represents a major roadblock to the treatment of brain disease. Researchers at Canada's Sunnybrook Health Sciences Center liken it to cling wrap, sealing the contents of the brain's small blood vessels and preventing the majority of foreign molecules from entering. Scientists have made some headway in trying to open the door, with recent studies on mice involving magnetic nanoparticles, microscopic bubbles and ultrasound techniques returning promising results.
It is the latter two of these tools that Sunnybrook scientists used in their groundbreaking experimental approach on a human subject. Suffering from a malignant brain tumor, the patient had already been scheduled for traditional neurosurgery to remove the lesion. But the day before the procedure, the team first introduced a small dose of chemotherapy into her bloodstream through an IV drip in her arm, and then added harmless microscopic bubbles to the mix.
With the drugs and bubbles both circulating through the patient's bloodstream, the team then targeted vessels in the blood-brain barrier close to the tumor using MRI-guided low-intensity ultrasound. The sound waves produced by the ultrasound served to compress and expand the microbubbles over and over again, resulting in vibrations that tore apart the tightly woven cells in selected areas of the barrier. This cleared the way for the chemotherapy drugs to pass through into the targeted region of the brain.
"Some of the most exciting and novel therapeutics for the treatment of malignant brain tumours are not able to reach the tumour cells because of the blood brain barrier," says Dr. Todd Mainprize, principal investigator of the study. "This technique will open up new opportunities to deliver potentially much more effective treatments to the targeted areas."
The team says that the blood-brain barrier remained opened for up to 12 hours and then began to repair itself. In the subsequent surgery less than 24 hours later, the tumor and surrounding tissue were removed and handed over to pathologists to study the concentrations of chemotherapy in an attempt to determine how much made it through to each of the ultrasound-targeted and non-targeted areas.
As part of this pioneering study, the scientists will test the approach on nine more human subjects, who are also in line for surgical tumor removal. They will be looking to establish the feasibility, safety and preliminary efficacy of the approach. If it proves a success, then the technique could not only open up new ways to tackle brain tumors, but other disorders where the blood-brain barrier has historically been a stumbling block. These include Alzheimer's, Parkinson's and other psychiatric conditions.
You can hear from Mainprize and get an overview of the process in the video below.