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Now Fight Iron Disorders With a Drug Against Hypertension

ar investigations, Weiss and his collaborators found out that nifedipine exerts its effect on iron metabolism by acting on a molecule called DMT-1. DMT-1 transports iron across cell membranes. This transport is increased ten to 100-fold by nifedipine, but how exactly the compound brings about its effect is still unknown. Nifedipine is known to block membrane channels that control Ca2+ influx into cells, but if it exerts its effect on iron transport indirectly by changing Ca2+ levels in the cell or by binding directly to DMT-1 in liver and kidney still needs to be determined.

"Understanding the exact molecular mechanism underlying nifedipine's effect on iron transport would be a big step towards developing it into an effective therapy that can be used on patients," says Martina Muckenthaler, an EMBL alumna who is now at the University of Heidelberg. "Taking nifedipine from bench to bedside could be quicker than for other substances, because it has already been used for years to treat patients with high blood pressure. From this we know the drug and its sideeffects."

An important step on the way from laboratory to clinic will be targeted pharmacological modifications of the compound to separate nifedipine's effect on iron metabolism from its established action on blood pressure.

"Our discovery is an excellent example of how the combination of basic research and the expertise of clinicians can yield results that are relevant to medicine and could ultimately benefit patients," says Matthias Hentze, Associate Director of EMBL and co-author of the study. "In the Molecular Medicine Partnership Unit [MMPU] between EMBL and the Medical Faculty of Heidelberg University we integrate molecular biology and clinical medicine to gain an understanding of the basis of human diseases. It is very gratifying to see how the collaboration with EMBL alumni and the MMPU yields exciting progress in medicine."

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