Researchers at Northwestern University (IL, USA) have demonstrated, using a mouse model, that ultrasound therapy could be an effective method for crossing the blood–brain barrier and treating glioblastoma. The study, published in Clinical Cancer Research, also revealed a new formulation of a standard drug that is both safer and more effective.
Though treatment options are available, glioblastoma currently has no cure. One obstacle to a successful long-term outcome in patients is the blood–brain barrier, which blocks current therapies from directly treating brain tumors. The current therapy, known as paclitaxel, is both unable to cross the blood–brain barrier and is toxic to the brain.
“Glioblastoma currently has no cure, and when the tumor recurs there are not many treatment options,” commented Adam Sonabend from Northwestern University, principle investigator for this study. “We urgently need effective new treatments.”
In this preclinical mouse study, researchers used a novel ultrasound technology allowing them to open the blood–brain barrier and directly treat the tumor. The procedure involves applying ultrasound to a window in the skull while simultaneously injecting microscopic bubbles into the blood. When the bubbles collide with the ultrasound waves, they vibrate and disrupt the blood–brain barrier, allowing the drug molecules to access the brain.
Further, research into the chemical formulation of the standard paclitaxel therapy revealed its toxicity to be due to the solution required to dissolve the drug, cremophor. The team observed that substituting cremophor for albumin eliminated toxicity of the drug.
Results from the lab revealed paclitaxel to be much more potent than the currently used chemotherapy temozolomide. Treating brain tumors with paclitaxel ex vivo revealed the concentration necessary to destroy a certain number of tumor cells to be 1400-fold lower, compared to the conventional chemotherapy used to treat this cancer.
The results of the ultrasound therapy revealed a fivefold increase in paclitaxel in the brain, along with extended survival among brain tumor-bearing mice that were treated with the combined paclitaxel and ultrasound.
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Co-investigator, Roger Stupp (Northwestern University), commented on the broader benefits of the therapy: “This ultrasound technology now will enable us to use many agents established in other cancers for patients with brain tumors.”
Further studies are now underway to test the ultrasound-based opening of the blood–brain barrier with various other chemotherapy agents.