Ultrasound trial offers hope for brain cancer patients
A technique has been developed that could revolutionise 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 in four women whose breast cancer had spread to the brain showed that magnetic resonance-guided focused ultrasound (MRgFUS) could safely deliver the antibody therapy Herceptin into their brain tissue, causing the tumours to shrink.
The blood brain barrier is a cellular wall designed to prevent substances in the bloodstream, such as toxins or microbes, from getting into the brain where they could cause irreparable damage to its tissues.
Whereas in the rest of the body there are tiny gaps between the cells lining the blood vessels that allow small substances to pass through, in the brain these spaces are fused, meaning that only water, certain gases such as oxygen, a handful of other necessary substances, and small fat-soluble drugs such as antidepressants get through.
“Many, many people have been trying lots and lots of different ways of getting stuff across the blood brain barrier, but it has proved to be extremely difficult – certainly to do it in a way that is temporary, said Eleanor Stride, a professor of biomaterials at the University of Oxford, who was not involved in the research.
“There’s a huge range of drugs that it would be good to get across, not just for [metastatic breast cancer], but for neurodegenerative diseases such as Alzheimer’s and other types of brain cancer as well.”
MRgFUS uses focused ultrasound (sound waves) to open the blood brain barrier in specific regions by causing microscopic bubbles of contrast agent that have been injected into the patient to oscillate. These oscillations pull apart the cells of the blood brain barrier, allowing substances that usually struggle to penetrate the brain to pass through.
Dr Nir Lipsman, of Sunnybrook Health Sciences Centre 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 is cocirculating in the bloodstream will gain access to the brain pathology (disease), where we want it to go.”
Lipsman and his colleagues had
previously shown that MRgFUS could be used to temporarily open the blood brain barrier in people with a different type of brain cancer or the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but they stopped short of using it to transport drugs into their brains
Now they have 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 the drug was taken up by the tumours and that they shrank in response – although the trial was primarily designed to assess safety.
Importantly, none of the patients experienced any serious adverse events, and further imaging suggested their blood brain barriers resealed after 24 hours.
“It has long been theorised that focused ultrasound can be used to enhance drug delivery, but this is the first time we have shown we can get drug into the brain, and the first time we have visualised it getting into the brain,” Lipsman said.
“Herceptin is also a huge compound, so if we can [get it in] we can pretty safely assume that we can get other compounds that are as large, or smaller, into the brain with focused ultrasound as well.”
Kevin O’Neill, a consultant neurosurgeon at the Brain Tumour Research Centre of Excellence at Imperial College London, said: “Many therapies that are coming through for brain cancer need a delivery system that not only packages and protects them but directs them to the correct area.
“Injecting them into the brain is one way, but this approach would be better because it is effectively non-invasive. You are kind of opening a portal in the blood brain barrier at the desired site. It’s a step forward to opening the door to other therapies.”