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A majority of the small and large molecule drugs can't penetrate the blood-brain barrier, which results in all central nervous system diseases being undertreated. The drugs can reach the brain by direct injection but that involves anesthesia and drilling the skull, which increases the risk of infection and limits the number of sites of injection.Focused ultrasound combined with microbubbles — gas-filled bubbles coated with protein or lipid shells — is currently the only technique that can penetrate the blood-brain barrier non-invasively. The microbubbles are hit by the ultrasound beam and they begin to oscillate and either continue to oscillate or collapse, depending on the amount of pressure.Even though that method is shown to be successful for delivering therapeutic drugs through the blood-brain barrier, it has only been used with one specifically-sized molecule. Researchers at Columbia University's Fu Foundation School of Engineering and Applied Science set out to find a way to control the size of the molecules so they can better penetrate the blood-brain barrier and deliver drugs even more effectively.Elisa Konofagou, the principal investigator and professor of biomedical engineering and radiology at the university, and her team found that higher acoustic pressures lead to larger molecules accumulating in the hippocampus and lower pressure leads to smaller molecules accumulating."All these drugs — small molecule or large molecule — don't penetrate, so with the lower pressure you can prevent the large molecules from going in when you're trying to have small molecules go through or you can increase the pressure to make sure the larger molecules can go in," Konofagou told DOTmed News.She believes that one of the most remarkable things about the technique is that it can regenerate the neurons, which is something that has never been done before. "Regenerating neurons in those diseases is a big achievement if you can get there," she said.Konofagou has been working on the technique for a decade now and has done mouse and monkey experiments with it. "We've shown safety — you can open the barrier and close it," she said.The next step is to try it out on humans; the only thing stopping them is the fact that the drugs are expensive for clinical use. But Konofagou is confident that within the next five years they will be able to perform the clinical trials.