Ultrasound implant helps potent cancer drug cross blood-brain barrier
A new study from Northwestern University is demonstrating evidence a novel implantable ultrasound device allows a less toxic formulation of chemotherapy to cross the blood-brain barrier and destroy deadly tumors.
The blood-brain barrier is an extremely important protective structure that keeps blood-borne pathogens from infecting our brains. For most people, a strong blood-brain barrier is a good thing, but for those suffering from aggressive brain cancers such as glioblastoma, it actually hinders clinicians' efforts to destroy tumors.
The challenge scientists face is getting the cancer-killing drugs through the blood-brain barrier so they can destroy the tumors. An interesting technique to disrupt the blood-brain barrier (BBB) some researchers have begun to experiment with is using focused ultrasound to temporarily open the BBB. Combining a pulsed ultrasound with an intravenous injection of microbubbles has been shown to transiently weaken the BBB, however, targeted penetration of a thick human skull with ultrasound waves has proved challenging.
An alternative technique, more recently developed, is to surgically implant an ultrasound emitter into a window in the skull. This enables the ultrasound waves to be precisely targeted without having to travel through bone.
Several clinical trials are already underway to test the safety and efficacy of this particular method in human subjects, particularly in the administration of chemotherapy agents to treat brain cancer. The implanted ultrasound technique is proving effective at mechanically disrupting the BBB for several hours, allowing a window for intravenously administered chemo drugs to penetrate into the brain.
New research from Northwestern University is offering promising evidence this implantable ultrasound technique could be effective in combination with one of the most potent chemotherapy drugs available. The study, published in the journal Clinical Cancer Research, reports extensive preclinical findings demonstrating a new formulation of a drug called paclitaxel can effectively kill glioblastoma in conjunction with the new ultrasound technique.
Paclitaxel is a potent cancer-killing drug used to treat a number of different solid tumor cancers. The drug has unfortunately never been that useful for glioblastoma due to its inabilty in crossing the BBB, and its high propensity to be toxic in the brain.
The new Northwestern research demonstrates a novel, less toxic, formulation of paclitaxel, delivered in conjunction with the implanted ultrasound device results in a five-fold increase in levels of the drug reaching the brain.
Early mouse studies found the new method significantly increases the lifespan of animals with brain tumors, and laboratory studies on tumor cells also discovered concentrations of the drug needed to kill the cancer were 1,400 times lower than what is currently needed through conventional chemotherapy. What this means is that the new method could be much more effective in targeting and destroying brain cancers, while also using lower concentrations of a drug that can have toxic side effects.
The Northwestern research team is currently applying to the FDA to conduct a human clinical trial testing its novel method in a cohort of patients. It's hoped such a trial, alongside several others already underway, will validate the efficacy of this implanted ultrasound technique. If successful, new clinical treatments could be available for one of the deadliest forms of cancer in a matter of a few years.
The new research was published in the journal Cancer Clinical Research.