News Vitamin B12 transport system can carry Gilenya into the brain: Study Vitamin B12 transport system can carry Gilenya into the brain: Study Finding 'supports creating brain-targeted B12 formulations' for MS by Marisa Wexler, MS | December 14, 2023 Share this article: Share article via email Copy article link The molecular process that brings vitamin B12 into the brain can also transport Gilenya (fingolimod), an approved treatment for multiple sclerosis (MS), according to a new study. The finding “supports creating brain-targeted B12 formulations” for MS, said Jerold Chun, MD, PhD, co-author of the study at Sanford Burnham Prebys, in a press release. āAugmenting brain B12 with [Gilenya] or potentially related molecules could enhance both current and future MS therapies. … In the future, this mechanism might also extend to novel treatments of other neuroinflammatory and neurodegenerative conditions,” Chun said. The study, “FTY720 requires vitamin B12-TCN2-CD320 signaling in astrocytes to reduce disease in an animal model of multiple sclerosis,” was published inĀ Cell Reports. Recommended Reading March 30, 2023 News by Lindsey Shapiro, PhD Bacterial toxin epsilon in gut may be environmental driver of MS Gilenya can reduce number of inflammatory cells that get into brain Gilenya is an approved oral therapy that helps to block the activity of a protein called S1P receptor. This protein is expressed by several types of inflammatory immune cells, and it’s been established that Gilenya and other S1P modulators can reduce the number of inflammatory cells that get into the brain to cause MS-driving damage. While reducing inflammation is thought to be Gilenya’s main mechanism of action, the S1P receptor protein is also found in several types of cells in the brain, including astrocytes ā star-shaped brain cells that normally support nerve function, but also may play a role in driving MS. Notably, animal studies have suggested Gilenya’s efficacy is also associated with its ability to block the S1P receptor on astrocytes. Now, researchers at Sanford Burnham Prebys and colleagues have conducted a series of experiments to further characterize the effects of Gilenya on astrocytes. Augmenting brain B12 with [Gilenya] or potentially related molecules could enhance both current and future MS therapies. The researchers found Gilenya treatment led to an increase in levels of CD320 in astrocytes. CD320 is a receptor protein that’s used to bring vitamin B12, an essential nutrient, inside the cell where it can be used. The B12 vitamin specifically binds to a “chaperone” protein called TCN2, and then CD320 moves the B12-TCN2 complex into the cell. Working in a mouse model of MS, the researchers showed Gilenya became much less effective when the mice were fed a diet lacking B12 or when they were engineered to lack the CD320 protein. Mice lacking B12 or CD320 also had more severe disease, and analyses of brain tissue from people with MS indicated that CD320 levels were reduced in areas of disease-related damage. Collectively, these findings imply a connection between the efficacy of Gilenya and the molecular machinery that transports B12 into brain cells. In further experiments, the researchers found Gilenya is able to stick to the chaperone protein TCN2, and this led to increased activity of the CD320 transport system bringing TCN2 into cells. Recommended Reading March 31, 2023 Columns by Ed Tobias That UTI ā was it caused by MS or was it the meat? B12 supplementation may increase benefits of Gilenya In short, the data from this study suggest Gilenya can hitch a ride into the brain on the same molecular machinery that usually brings B12 into cells, and that B12 supplementation may increase the benefits of Gilenya treatment. This finding adds to growing evidence that Gilenya may have direct effects on brain cells that contribute to its efficacy in MS, the researchers said. They highlighted a need for further studies to verify this idea and see if other S1P receptor modulators have similar properties. Of note, B12 deficiency is known to cause a syndrome characterized by neurological symptoms similar to what’s typically seen in people with MS. The discovery of this molecular pathway may provide insight into why this is the case. āThe shared molecular binding of the brainās vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, with the FDA-approved MS drug [Gilenya] provides a mechanistic link between B12 signaling and MS,ā Chun said. Print This Page About the Author Marisa Wexler, MS Marisa holds a Master of Science in cellular and molecular pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. Her areas of expertise include cancer biology, immunology, and genetics, and she has worked as a science writing and communications intern for the Genetics Society of America. Tags Gilenya
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