Novel molecular shuttle could expand delivery of medicines across the blood–brain barrier
The blood–brain barrier (BBB) is a protective filter that lines the brain's blood vessels and is notoriously hard to penetrate, making the treatment of brain disorders very difficult. Strategies designed to breach the BBB include using brain surgery and focused ultrasound waves to create physical openings for the transportation of medicines and employing engineered adeno-associated viruses (AAVs)…
The blood–brain barrier (BBB) is a protective barrier that lines the brain’s blood vessels, making it difficult to deliver medicines to treat neurological and neuropsychiatric disorders. Researchers at Caltech have developed a novel method called BrainCAB (Brain access through Carbonic Anhydrase-binder Bioconjugation) to overcome this challenge.
This method utilizes a small molecule called brinzolamide, which is commonly used to treat glaucoma, to act as a molecular shuttle that can bind to a receptor called carbonic anhydrase IV (CA-IV) on the BBB. By modifying brinzolamide, the researchers were able to create a shuttle that can carry a wide range of therapeutics across the BBB, including antibodies, proteins, and RNA medicines.
The BrainCAB shuttle has been shown to effectively deliver atezolizumab, an immunotherapy used to treat various cancers, to the brain in both rodents and nonhuman primates. This new approach not only increases the amount of therapeutic reaching the brain but also enhances the persistence of its effects compared to existing delivery methods.
The modular chemistry of the BrainCAB shuttle may simplify its manufacturing and make it adaptable for various therapeutic applications.
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