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    Home > Medical News > Medical World News > Macromolecules break through blood-brain barrier, scientists make important progress

    Macromolecules break through blood-brain barrier, scientists make important progress

    • Last Update: 2020-06-15
    • Source: Internet
    • Author: User
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    This week, Science Translational Medicine, a sub-journal of Science, reported on two research papers published by Denali TherapeuticsIn the paper, the biotech company introduces a new technology that can help macromolecules break through the blood-brain barrier and enter the brainIt also means that, after more than 40 years of continuous experimentation, we have finally made encouraging progressWhen it comes to the history of the blood-brain barrier, it goes back more than 100 yearsAt the time, Paul Ehrlich, a late Nobel Laureate, was studying how to dye different tissues and organsHe found that after the dye was injected, the organs of some animals were coloured, with the exception of the brainHe attributes the reason simply to the lack of absorption in the brainLater, one of his students did another experiment, injecting the dye directly into the cerebrospinal fluid of the animal's brainThis time, he observed the opposite: brain tissue was perfectly dyed, but the rest of the body was not coloredBased on these findings, scientists at the time concluded that there was a mysterious barrier between the central nervous system and other parts of the body that prevented the free flow of matterAt first, it was thought that the barrier effect was caused by blood vesselsNow we know that the blood-brain barrier is made up of closely connected endothelial cellsBecause of the blood-brain barrier, many biomolecules are unable to enter the brain from the blood circulation, limiting the use of many drugs -- and if they can't get into the brain, naturally they can't treat diseases in the brainSince then, many scientists have been exploring ways to break through the blood-brain barrierThis exploration is decades awayIn the 1980s, Professor William Banks of the University of Washington came up with a "Trojan horse"-style ideaWe already know that certain macromolecules can be transported to the brain by binding specific receptors on the blood-brain barrier The discovery has inspired scientists - if we connect some antibody/antibody fragments to macromolecules with therapeutic potential, and these antibody/antibody fragments fit into specific receptors on the blood-brain barrier, can we sneak these macromolecules into the brain? This strategy sounds simple, but it's very difficult to implement Forty years on, people have not been successful in their exploration "I sometimes think that the idea of a 'Trojan horse' might tempt drug companies into a dead end, " Professor Banks said in a report in the American Chemical Society's c.EN magazine The two papers, published in the sub-journal Science, suggest that this dead end is over Let's go back to Denali Therapeutics The company's founder, Dr Ryan Watts, led research in neuroscience at Genentech, pushing macromolecules across the blood-brain barrier, the direction he has worked on for more than a decade In the first paper, the company's researchers developed a new technology They use fc fragments of antibodies and constantly induce them to mutate until they bind to the "transferrin receptor" on the blood-brain barrier As the name suggests, under normal circumstances, this receptor is responsible for transporting iron-containing "iron-carrying" into the brain And when the mutant Fc fragment sin-binds to the ferrite receptor, it has the potential to be transported into the brain by the latter If you attach macromolecule drugs to this Fc fragment again, won't you get them a lift and get into the brain? To test the feasibility of the idea, the scientists tested the Fab fragment spent targeting BACE1 with the Fc fragment mentioned above BACE1 is an enzyme involved in beta-amyloid protein formation, which is thought to inhibit BACE1, which inhibits the production of beta-amyloid protein deposits In mice and monkeys, scientists found that these newly designed fusion proteins were effective in breaking through the barriers of the blood and brain and reducing beta-amyloid levels in the brains of these animals The results also provide a conceptual validation of this technology There had been hopes of treating Alzheimer's disease with BACE1 inhibitors, but several clinical trials failed So the first study was more like a proof of concept, with clinical applications relatively unclear To assess the potential of this technology to treat human patients, scientists conducted a second study Specifically, they connected an enzyme called IDS to the Fc fragment, hoping to send them into the brain to treat Hunter Syndrome syndrome, which is caused by a lack of the enzyme The results of the mouse experiment showed that the addition of Fc fragments to the brain by 20 times compared to injecting the enzyme directly into the blood! In addition, these enzymes can also play a biological role, effectively reducing the level of the brain's substrate It's worth noting that the researchers observed the distribution of the enzyme throughout the brain and supported the potential of this delivery method from the side Next, Denali hopes to use this innovative technology to treat human patients with Hunter's syndrome The clinical trial is scheduled to begin in June If clinical trials are successful, they will undoubtedly be used in more similar diseases " (Breaking the blood-brain barrier) was once a very frustrating area But I think in both of these papers, they played a nice home run Professor Banks commented As stated in the second paper, the data highlight the potential of this technology to help macromolecule drugs break through the blood-brain barrier We also look forward to these preclinical results, which can be repeated in human patients and lead to new treatments for many brain diseases.
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