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| Innsbruck/Heidelberg, 11 February 2007 |
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| Putting an old drug to a new use
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Researchers discover how to fight iron disorders with a drug against hypertension
Press
Release 11 February 2007 [PDF]
We all know that
iron deficiencies are dangerous, but also too much iron is bad for
our health. Our body stores excess iron in various tissues, where
it can lead to organ failure and even death if not treated before
irreversible damage has occurred. Researchers from the
Innsbruck Medical University, the University of Heidelberg,
Germany, and the European Molecular Biology Laboratory
[EMBL] now made a surprising discovery that may lead to new
therapeutic approaches to treating such disorders. In this week's
online issue of the journal Nature Medicine they report that a
compound that was frequently used to treat high blood pressure
can reverse iron overload in mouse models and has the potential
to treat similar conditions in humans.
Our body needs most of its iron to make red blood cells. A lack of
the metal can lead to dangerous anemias, but also too much iron
can be detrimental as iron promotes the formation of toxic radicals
leading to tissue damage. Iron overload is the consequence of
one of the most common genetic disorders in Europe, hereditary
hemochromatosis, which affects about one in 300 Europeans.
Excess iron also accumulates after repeated blood transfusions
and can cause organ failure over time. Günter Weiss, a clinician
from the Innsbruck Medical University, and his collaborators
from the University of Heidelberg and EMBL now found out that
nifedipine, a substance commonly used to control blood pressure,
helps the body deal with too much iron.
"We observed in mice with iron overload that nifedipine helps
mobilise iron from stores in the liver and enhances its excretion
into the urine," says Weiss, an EMBL alumnus who now heads a
lab at the Department for General Internal Medicine at the
University of Innsbruck. "These effects make nifedipine a promising
candidate for a new drug to treat hereditary hemochromatosis
and other iron overload disorders."
Combining electrophysiology, cell biology and molecular 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."
Source Article
S. Ludwiczek, M.U. Muckenthaler, M.W. Hentze, G. Weiss et al. Ca2+ channel blockers reverse iron overload by a novel mechanism
via divalent metal transporter-1, Nature Medicine, 11 February 2007
Press Contacts
Anna-Lynn Wegener
Press Officer
EMBL Heidelberg
Tel: +49 6221 387-8452
Email: wegener@embl.de
Uwe Steger
Press Officer
Innsbruck Medical University
Tel: +43 512 9003-70080
Email: uwe.steger@i-med.ac.at
Annette Tuffs
Press Officer
University Clinic Heidelberg
Tel: +49 6221 564536
Email: Annette_Tuffs@med.uni-heidelberg.de |
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