A technology has been developed that could revolutionize the treatment of brain cancers and neurodegenerative diseases by temporarily allowing drugs and other substances to cross the blood-brain barrier – a structure that separates the brain’s blood vessels from the rest of its tissues.
A trial of four women whose breast cancer has spread to the brain shows that magnetic resonance-guided focused ultrasound (MRgFUS) can safely deliver Herceptin antibody therapy to brain tissue, shrinking tumors.
The blood-brain barrier is a cell wall designed to prevent substances in the bloodstream, such as toxins or microbes, from entering the brain where they can cause irreparable damage to its tissues.
While in the rest of the body there are small gaps between the cells lining the blood vessels that allow the passage of small substances, these spaces are incorporated into the brain, which means that only water, certain gases such as oxygen, and a handful of other necessary gases, substances and small fat-soluble drugs such as Antidepressants.
said Eleanor Stride, a professor of biomaterials at Oxford University, who was not involved in the research.
“There are a whole lot of medicines that would be nice to have, not just for her [metastatic breast cancer], but for neurodegenerative diseases like Alzheimer’s and other types of brain cancer as well.”
MRgFUS uses focused ultrasound (sound waves) to open the blood-brain barrier in specific areas by causing microscopic bubbles of the contrast agent injected into the patient to vibrate. These oscillations break down the cells of the blood-brain barrier, allowing substances that would normally struggle to penetrate the brain to pass through.
Dr. Nir Lipsman, of Sunnybrook Health Sciences Center in Toronto, Canada, who led the study, said: ‘This is a temporary process where the blood-brain barrier is opened for less than 24 hours. The idea is that whatever goes in the bloodstream will get into the pathology of the brain. (illness), where we want him to go.”
Lipsmann and colleagues previously showed that MRgFUS could be used to temporarily open the blood-brain barrier in people with a different type of brain cancer or neurodegenerative amyotrophic lateral sclerosis (ALS), but they stopped using it to transfer drugs to it. their brains
They have now used it to deliver the monoclonal antibody trastuzumab (Herceptin) to diseased areas of brain tissue in four patients with metastatic breast cancer.
The research, published in Science Translational Medicine, showed that tumors had taken up the drug and had shrunk in response – although the trial was designed primarily to assess safety.
Importantly, none of the patients experienced any serious adverse events, and further imaging suggested that their blood-brain barriers re-closed 24 hours later.
“It’s long been assumed that focused ultrasound can be used to enhance drug delivery, but this is the first time we’ve shown that we can get a drug into the brain, and the first time we’ve visualized it getting into the brain,” Lipsman said. .
“Herceptin is also a huge compound, so if we could [get it in] We can safely assume that we can introduce other compounds that are large or smaller into the brain using focused ultrasound as well.”
Kevin O’Neill, Consultant Neurosurgeon at the Center of Excellence for Brain Tumor Research at Imperial College London, said: “Many of the treatments that come in for brain cancer need a delivery system that not only packages and protects it, but also directs it to the right treatment area.
“Injecting them into the brain is one way, but this approach would be better because it is effective, non-invasive. You kind of open a gate in the blood-brain barrier at the desired location. It’s a step forward to open the door to other treatments.”