Breaching the blood-brain barrier

After managing her brain tumour with medication for the past eight years, “It’s starting to grow, you need to see somebody” are not the words Bonny Hall wanted to hear.

Dr. Todd Mainprize, the leading investigator in a ground-breaking clinical trial identified that the medication was no longer able to reach the tumour cells in her brain because of the blood-brain barrier. Scientifically speaking it is a semi-permeable membrane separating the blood from the cerebrospinal fluid, a colourless liquid that protects our body’s central nervous system. Think of it as extremely overprotective parents, parents who never allow their children to go out and explore freely thus making sure they never get hurt but at the same time discouraging them from encountering things that may be beneficial. The barrier does an exceptional job but is so effective at keeping out foreign substances that it often prevents life-saving drugs from being able to heal the injured brain.

“To help guide ultrasound waves or sonication to precise areas in her brain, Bonnie was fitted with a helmet-like device and placed inside an MRI”

There have been many experimental attempts in the past to penetrate this barrier but for the first time in history, doctors and scientists at Toronto’s Sunnybrook Hospital successfully attempted to open this blood-brain barrier in a human without the use of a scalpel. This innovative and non-invasive technique was to essentially create holes in the blood-brain barrier so that various selected chemicals can get through.

The process began when Bonnie was treated with chemotherapy, followed by an injection of microscopic bubbles or little bits of air that would circulate in her bloodstream. To help guide ultrasound waves or sonication to precise areas in her brain, Bonnie was fitted with a helmet-like device and placed inside an MRI. The aim was that this would cause the microscopic bubbles to shake and create small temporary holes in the barrier.

A few hours later, the doctors have finished the sonication for two spots and they have opened up the barrier in both spots. The next step was to verify an array of nine dots on an MRI scan in each of the places the barrier was opened. After examining the scan Dr. Mainprize says, “This had gone exactly the way we hoped”— the eight most reassuring words for Bonny and her family to hear. The identification of those nine dots indicated an effective opening of the blood-brain barrier and hence marked this procedure to be a huge success. Finally, the rest of the tumour was removed during surgery and then examined to see exactly how much medication got through.

“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,” said Dr. Mainprize. This new treatment will not only help people suffering from illnesses like Bonnie’s but also a vast number of other patients with brain cancer, Parkinson’s, Alzheimer’s, and so on. An estimated 98% of potential drug treatments for brain disorders are unable to penetrate the blood-brain barrier. Consequently, there are limited options for patients with brain tumours and other neurological diseases. The barrier has posed as a constant obstacle to treating countless types of brain disorders, therefore, “breaching this barrier opens up a new frontier in treating brain disorders,” says Dr. Neal Kassell, chairman of the Focused Ultrasound Foundation.

“An estimated 98% of potential drug treatments for brain disorders are unable to penetrate the blood-brain barrier”

Bonnie’s bravery, along with that of the team of skilled professionals at Sunnybrook hospital has set a significant milestone in medical history. This trial will include 6-10 more patients over the course of the next few months in Canada to make absolutely sure that the blood-brain barrier is safe to penetrate in humans. Given that the procedure is effectively a highly focused ultrasound and only acts to temporarily open up the blood-brain barrier, scientists are confident that this treatment is safe and will open up a whole host of new doors for effective and targeted therapies for a large range of brain disorders.

Bringing it back to the analogy of overprotective parents, it seems as though we have been able to find a way to convince them. This was an exciting procedure that resulted in a positive outcome. Allowing medication to seep directly into parts of the brain will be invaluable to the advancement of treatments for other brain-related diseases. Yesterday, the blood-brain barrier seemed impossible to tackle; today, it might not be beyond the bounds of human ability after all.

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