Confirmed for the first time in the world!

▎ WuXi AppTec content team editor When you read this article, a war against foreign enemies is quietly unfolding in your brain
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In our brain, the blood vessel wall composed of endothelial cells is like a city wall, blocking the path of viruses, bacteria and other toxic substances into the brain
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But when we hope to deliver drugs to the brain, this line of defense called the "blood-brain barrier" still fulfills its responsibility to resist foreign objects-only this time, it blocks the opportunity for drugs to treat brain diseases
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Compared with the risks of injecting drugs directly into the brain, researchers have always hoped to find a way to temporarily open the blood-brain barrier without damage, so as to deliver drugs to the brain
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In the new issue of "Science Translational Medicine" (Science Translational Medicine), a study led by scientists at the Sunnybrook Health Science Center in Canada used a clever method to cross the blood-brain barrier and target cancer in the brains of cancer patients.
The cell launched an attack
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 The subjects in this phase 1 clinical trial are 4 HER2-positive breast cancer patients between the ages of 31 and 56
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The cancer cells of these patients have spread to bones, liver and other organs-of course, the brain is not immune
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Before starting the clinical trial, they were receiving treatment with a monoclonal antibody called trastuzumab
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Previous studies have confirmed that this antibody therapy combined with radiotherapy or chemotherapy has achieved a good therapeutic effect on HER2-positive breast cancer.

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But as mentioned at the beginning, these antibodies can work in other organs, but it is difficult to enter the brain
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To solve this problem, the solution used by the research team is Magnetic Resonance Guided Focused Ultrasound (MRgFUS)
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Simply put, it is to first inject micro-lipid bubbles into the blood vessel.
When the ultrasound beam irradiates a specific area, the bubbles in the blood vessel will shake slightly, making the blood vessel wall less firm
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For the research team, their target area is naturally the blood-brain barrier-once MRgFUS temporarily increases the permeability of the blood-brain barrier, the monoclonal antibodies in the vein have the opportunity to enter and reach the brain tumors
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Previous preclinical studies have found that applying this idea to the blood-brain barrier can allow monoclonal antibodies to enter the brain; however, the efficacy of this new therapy in the brain has not been tested
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The work carried out by Sunnybrook Health Sciences Center is the first time that the effectiveness of this therapy has been tested in a clinical trial
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The researchers provided four patients with a normal dose of trastuzumab, but it was mixed with a small amount of radioactive elements to label the content of the antibody in the brain
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As a result, after using MRgFUS, the radiolabel content in the brain doubled on average, which proves that more trastuzumab enters the brain
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Magnetic resonance imaging in the next few days also confirmed that the blood-brain barrier was closed again
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 ▲After 4 hours (left) and 48 hours (right) using MRgFUS, the changes in the blood-brain barrier (picture source: reference) After that, the detection of changes in the volume of brain tumors initially demonstrated the effectiveness of the treatment: 4 After all patients received treatment, the volume of brain tumors decreased, with an average reduction of 22%.
Among them, the tumor was reduced by 31% in the most effective patient
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 ▲The changes in brain tumor volume after 4 patients received treatment (picture source: Reference [1]) Of course, subject to the scale of this clinical trial, researchers are still cautious about the research itself
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But they believe that this idea has far-reaching significance for future research
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Dr.
Nir Lipsman, who led this research, believes that although this research is very preliminary, it shows attractive prospects
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After all, the existence of the blood-brain barrier is a huge obstacle to any drug therapy that targets the brain
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"Follow-up research is not only expected to have an impact on the treatment of brain tumors, but also to bring dawn to the treatment of other neurological diseases such as Parkinson's disease and Alzheimer's disease
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"References: [1] (2021) MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases.
Science Tranlational Medicine DOI: 10.
1126/scitranslmed.
abj4011[2] World-first clinical trial demonstrates focused ultrasound can deliver antibody therapy to breast cancer metastases in the brain.
Retrieved Oct.
14, 2021 from https:// Sound Waves Aid Brain Tumor Treatment.
Retrieved Oct.
14, 2021 from https: //