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Tuesday, September 27, 2016 Posted by: Elizabeth Porco
How the multiple sclerosis (MS) therapy Tecfidera (dimethyl fumarate) works on a molecular level has finally been uncovered, using a new method that can map a drug’s protein targets. The insights gained may open up new avenues for the development of more specific drugs, based on the same mechanisms, but with fewer side effects.The study, “Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells,” was published in the journal Science Signaling.“This new technology has given us insights into the therapeutic modulation of the immune system that we could not have obtained with standard approaches,” John R. Teijaro, an assistant professor at The Scripps Research Institute (TSRI) and co-senior author of the study, said in a news release.Although Tecfidera is the most widely prescribed MS drug available as a pill, researchers have not really understood exactly how it works. This is often the case for drugs that have been around for a while, and dimethyl fumarate is also the main component of the psoriasis drug Fumaderm, which has been used successfully since the 90s. (Tecfidera was approved for relapsing MS by the U.S. Food and Drug Administration in 2013).Many earlier studies attempted to determine how Tecfidera slows relapse rates in MS, and scientists have suggested that a protein called Nrf2 is the treatment’s main target. The idea is that Tecfidera activates Nrf2, which, in turn, unleashes a forceful antioxidant response. But more recent investigations pointed to it mostly working to reduce the activation of the immune system.
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