Science Translational Medicine, a sub-journal of Science, also reports on two research papers published by Denali SpasIn the paper, the biotech company introduces a new technology that could help macromolecules break through the blood-brain barrier and enter the brainIt also means that after more than 40 years of continuous trial, we have finally made welcome progressmysterious brain barrier
the history of the blood-brain barrier goes back more than 100 yearsAt the time, Paul Ehrlich, a later Nobel laureate, was studying how to dye different tissues and organs with dyesHe found that after the dye was injected, some of the animal's organs were colored, with the exception of the brainHe simply attributes the reason to the brain's lack of absorptionlater, one of his students did another experiment in which dye was injected directly into the cerebrospinal fluid of the animal's brainThis time, he observed the opposite effect: brain tissue was perfectly dyed, but the rest of the body was not dyedbased on these findings, scientists at the time concluded that there was some mysterious barrier between the central nervous system and the rest 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 biological macromolecules are unable to enter the brain from the blood circulation, limiting the use of many drugs - and if they do not get into the brain, they will naturally not be able to treat diseases in the brainsince, many scientists have been exploring ways to break through the blood-brain barrierThis exploration is decades awayTrojan horse
Professor William Banks of the University of Washington came up with a "Trojan Horse" idea in the 1980swe already know that certain macromolecules can be transported to the brain by binding specific receptors on the blood-brain barrierThe discovery has inspired scientists - if we connect some antibodies/antibody fragments to large molecules with therapeutic potential that happen to bind to specific receptors on the blood-brain barrier, can we sneak through Chencang and sneak these macromolecules into the brain?this strategy sounds simple, but it's very difficult to implementForty years on, people have not succeeded in exploring"I sometimes think that the idea of a 'Trojan horse' might lure drug companies into a dead end, " says Professor Banks in a report in the American Chemical Society's C.EN magazine"
and these two papers, published in the journal Science, suggest that this dead end is clearhitchhiking technology
we're going back to Denali TherapeuticsThe company's founder, DrRyan Watts, who has led research in neuroscience at Genentech, has been working on macromolecules for more than a decade to break through the blood-brain barrierin the first paper, the company's researchers developed a new technologyThey use fc fragments of antibodies and constantly induce them to mutate until they bind to the "transportin receptor" on the blood-brain barrier As the name suggests, in general, this receptor is responsible for transporting iron-containing "transportferrin" into the brain and when the mutated Fc fragments bind to ferritin receptors, they have the potential to be transported into the brain by the latter If you connect macromolecule drugs to this Fc fragment, can't you get them on a lift and into the brain? to test the feasibility of the idea, scientists linked fab fragments targeted to BACE1 with the Fc fragments mentioned above and tested them BACE1 is an enzyme involved in the formation of beta-amyloid protein, which is thought to inhibit the production of beta-amyloid protein deposition by inhibiting BACE1 in mice and monkeys, scientists have found that these newly designed fusion proteins can effectively break through the blood-brain barrier and reduce beta-amyloid levels in the brains of these animals The results also validate the technology in concept hopes to treat Alzheimer's disease with BACE1 inhibitors have been hoped to be but several clinical trials have failed So the first study was more of a proof-of-concept, clinically unknown 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 feed it into the brain to treat Hunter Syndrome, which is caused by the enzyme's lack and the results of mouse experiments show edgy 20 times higher enzyme content in the brain than injecting the enzyme directly into the blood, adding fc fragments! In addition, these enzymes can also act biologically, effectively reducing the level of their substrates in the brain 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 syndrome The clinical trial is scheduled to begin in June If clinical trials successful, they will undoubtedly be used in more similar diseases (breaking the blood-brain barrier) used to be a very frustrating area But I think in those two papers, they played a nice home run Professor Banks commented (
Bio valley Bioon.com)