Scientists at Sunnybrook Health Sciences Center in Canada were able to breach the blood-brain barrier (BBB) to administer cancer drugs directly to a patient's brain tumor. The breakthrough is said to open up possibilities of more effective treatments for other neurological diseases such as dementia and Parkinson's disease.
The new technique was tested first on a patient named Bonny Hall, who was diagnosed with a malignant brain tumor called glioma. She managed her tumor via medications for eight years but earlier in 2015, she was told that the tumor had gotten bigger and needed more aggressive treatment. She was offered and eventually agreed to be the first patient to receive the experimental therapy that involves breaking through the BBB to deliver chemotherapeutic drugs.
During the procedure, experts monitored how the drug was delivered to Hall's tumor via functional Magnetic Resonance Imaging (fMRI) and according to the project's principal investigator Dr. Todd Mainprize, the modality went exactly as hoped. Hall's tumor was surgically removed thereafter and is now up for analysis to determine how much of the chemotherapeutic drugs were able to penetrate the tumor.
How Does It Work?
Initially, patients are administered with an intravenous cancer drug that cannot typically pass through the BBB. They then receive an infusion of microbubbles, which travel throughout the body including the blood vessels in the brain.
Patients next wear a cap that contains different transducers that drive ultrasound waves into the brain. Called high-intensity focused ultrasound, the procedure works just like a magnifying glass that can focus the sun's rays. The ultrasound waves are concentrated inside the body to force the microbubbles to vibrate.
The bubbles spread and contract approximately 200,000 times per second, which is enough to tear apart the endothelial cells that make up the BBB. This process allows cancer drugs to pass from the bloodstream to the BBB holes and finally into the tumor.
The ultrasound procedure commonly lasts for two minutes and within this period, about nine holes near the tumor will be made in the BBB of patients. Monitoring of drug movement via fMRI and surgical extraction of the tumor thereafter for analysis will be performed next.
Dr. Kullervo Hynynen, director of physical sciences at Sunnybrook Research Institute, said that the BBB will begin to close almost immediately after the ultrasound is switched off and it will go back to its pre-procedure state after six hours. As per animal studies, minimal side effects and no long-term impacts have been noted.
Applications To Other Brain Diseases
BBB restricts passage of substances from the bloodstream to the brain, protecting it from potentially hazardous substances. While it may sound highly beneficial, this is also what keeps doctors from administering drugs directly to the brain for more enhanced treatment of neurological diseases.
"The blood-brain barrier (BBB) has been a persistent obstacle to delivering valuable therapies to treat disease such as tumors," said Mainprize.
The success of the study will pave the way for administering drugs to brain parts that are well protected by the BBB. "Opening the barrier is really of huge importance. It is probably the major limitation for innovative drug development for neurosciences," said Bart De Strooper, co-director of the Leuven Institute for Neuroscience and Disease in Belgium.
Patients of other types of brain tumors, Alzheimer's disease and other brain disorders will benefit from this new treatment should it continue to exhibit promising trial results. Other diseases that do not primarily involve the brain may also be treated. For example, breast cancer drug trastuzumab cannot pass through the BBB and treat tumors that have metastasized to the brain. The procedure could be beneficial in these types of situations.
De Strooper said that it could also open up production of highly tailored drugs for an entire range of brain receptors, meaning coming up with treatments for clinical depression and schizophrenia.
"It's going to also look after things like epilepsy, Alzheimer's, a lot of other diseases," Hall said. "This isn't just about a brain tumor."