Posted on Jun 30, 2020, 3 p.m.
For the first time in a groundbreaking clinical trial a team of neurosurgeons.from Sunnybrook Health Sciences Center in Toronto, Ontario, Canada has penetrated the blood brain barrier non-invasively in a human patient named Bonnie Hill who had previously been managing her malignant brain tumor with medication before being given difficult news earlier this year of the continued growth.
“The blood-brain barrier (BBB) has been a persistent obstacle to delivering valuable therapies to treat disease such as tumours,” says Dr. Todd Mainprize, principal investigator of the study and neurosurgeon in the Hurvitz Brain Sciences Program at Sunnybrook Health Sciences Centre in a media release.
The blood brain barrier is a plastic like wrap coating around the small blood vessels in the brain, this barrier normally restricts passage of substances from the bloodstream from entering into the brain as well as protecting the brain from toxic chemicals. The BBB also does not allow most medication to pass through, which has several implications for many conditions including cancer, Parkinson’s disease and Alzheimer’s disease.
“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, who is the lead investigator, neurosurgeon at Sunnybrook, as well as an assistant professor in the Division of Neurosurgery at University of Toronto. “Our technique is to essentially tear holes in the plastic wrap and allow the various chemicals we want delivered to the brain, to get into the brain.”
The patient received chemotherapy which was later followed by an injection of microbubbles of air to circulate in her bloodstream. Bonny was then fitted with a specialized device on her head which was co-developed by Sunnybrook before being placed in an MRI to help guide the low intensity ultrasound waves to precise areas in her brain; this procedure caused the microbubbles to shake and temporarily make holes in the BBB allowing medication to seep into the tumor.
“We are encouraged that we were able to temporarily open this barrier in a patient to deliver chemotherapy directly to the brain tumour.”
“The trial has gone exactly the way we hoped,” says Dr. Mainprize. During the procedure, nine dots on the brain scan lit up, indicating the opening of the blood-brain barrier. “We are encouraged that we were able to temporarily open this barrier in a patient to deliver chemotherapy directly to the brain tumour. This technique will open up new opportunities to deliver potentially much more effective treatments to the targeted areas.”
According to Dr. Kullervo Hynyen who is the Director of Physical Sciences at the Sunnybrook Research Institute who worked for close to 2 decades with industry partner Insightec to develop this technology and bring it to a clinic ready state: “The success of this case is gratifying,” he says. “My hope now is that many patients will eventually benefit from it.”
The following day Bonny had surgery to remove part of the tumour and surrounding tissues which were sent to pathology for analysis to determine how much medication got it to. As the injected chemotherapy is taken out with the removal of the brain tumor, Bonny and the other participants of this research trial will not benefit from this particular focused ultrasound procedure.
“Research participants, like Bonny, are committing a truly selfless act to help research along so it may be able to help other patients in the future,” says Dr. Mainprize. “Thanks to Bonny and all other participants, this breakthrough opens up potential for delivering drug therapies to parts of the brain that were previously impenetrable because of the blood-brain barrier.”
Bonny was nervous and excited to be the first; “If I can help in any way, it’s going to be able to look after things like epilepsy, Alzheimer’s and a lot of other diseases. This isn’t just about a brain tumour.”
“We are very lucky at Sunnybrook to have a large interdisciplinary group of physicists, radiologists, neurosurgeons and oncologists that can work together and push this trial forward. We’re very honoured to be the first centre that’s able to do this,” says Dr. Mainprize.
“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 Mainprize. “This technique will open up new opportunities to deliver potentially much more effective treatments to the targeted areas.”
This trial will be extended to include another 6-10 patients over the next few months to make sure that opening the BBB like this is safe to penetrate in humans. All research participants are those who are already scheduled for traditional neurosurgery to remove parts of their brain, tumors and some surrounding tissues. Enrolment into this trial is limited to Canadian residents only due to it being an inpatient surgical procedure, which is being funded by The Focused Ultrasound Foundation through their Cornelia Flagg Keller Memorial Fund for Brain Research.
“Breaching this barrier opens up a new frontier in treating brain disorders,” says Dr. Neal Kassell, chairman of the Focused Ultrasound Foundation. “We are encouraged by the momentum building for the use of focused ultrasound to non-invasively deliver therapies for a number of brain disorders.”
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