Earlier this month, neurosurgeon Dr. Todd Mainprize and his research team at Sunnybrook Hospital in Toronto, Ontario successfully and non-invasively broke the blood brain barrier (BBB) using focused ultrasound.
We all have a BBB that highly regulates and prevents the entry of unwanted molecules (such as neurotoxins). Obviously, we wouldn’t want any neurotoxin getting past the BBB, so it’s very important to maintain its integrity. So how would one successfully deliver a chemotherapy drug to a brain tumour if we have this highly regulated system preventing the entrance of foreign substances into the brain?
In the last twenty years, scientists have been reporting on the use of ultrasound as more than just a diagnostic tool to image the fetus and abdomen of patients. Specifically, ultrasound can also be used as a therapeutic tool to enhance the delivery of molecules such as chemotherapy drugs across impermeable membrane barriers.
How it works
Ultrasound alone cannot effectively permeate biological membranes. Micron-sized bubbles, or “microbubbles”, are needed to facilitate the disruption of membranes. To give you perspective, a grain of beach sand is anywhere from 100 mm to 2000 mm, so we’re talking microscopic (pun intended)! The microbubbles themselves are smaller than red blood cells and harmlessly pass throughout the body. In an ultrasound field, these microbubbles will oscillate vigorously, where this mechanical disturbance causes nearby cell membranes to temporarily rupture. This transient permeation of membranes can allow surrounding chemotherapy drugs to now enter what was once an impermeable membrane.
Bonny Hall was the first of ten participants eligible to receive this novel treatment. The doctors at Sunnybrook tracked the progress of her therapy by analyzing pieces of the brain both treated and untreated with ultrasound and microbubbles. As hoped, they successfully enhanced the delivery of chemotherapy to the treated cells relative to untreated regions of the brain.
The use of focused ultrasound with microbubbles to open the BBB has been extremely successful in delivering foreign molecules to the brain in model organisms. It offers a targeted delivery of chemotherapy directly to the brain tumour while minimizing the systemic effects of the drug elsewhere in the body. The success of this therapy in patients will revolutionize the way brain malignancies are treated and open the doors towards targeted chemotherapy treatments.