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Iron in hemochromatosis: Deleterious effects of an essential nutrient
NUTRIENT IRON TOXICITY

Contract number : QLK1-2001-00444
Contract type : Shared Cost Project
Total cost : € 2.624.534
EC contribution : € 2.326.751
Starting date : 1/05/2002
Duration : 36 Months
Scientific Officer : Barend Verachtert
Project website : not yet available
Coordinator
Prof. Dr Joannes J.M. Marx
Universiteit Utrecht
Eijkman-Winkler Institute
University Medical Centre Utrecht
Heidelberglaan 100
3508 GA Utrecht
The Netherlands
Tel.: +31 302 50 73 94
Fax: +30 302 51 83 28
E-mail: jmarx @ azu.nl
Background

Normal dietary iron causes organ damage in patients with homozygous Hereditary Hemochromatosis (HH). Heterozygotes (10% of the European population) are at risk for early cardiovascular death. HH patients absorb too much iron and have toxic non-transferrin-bound iron (NTBI) in plasma. This project intends to identify the mechanism of TBI toxicity, and the damage to vascular endothelium (as target for atherosclerosis) and to the liver. An inexpensive method for NTBI measurement will be developed. Oral iron chelators will be developed to inhibit excess absorption of iron and to scavenge NTBI. Iron absorption, as a key pathogenic mechanism, will be analysed at a molecular level. The project is expected to result in less organ damage and in prevention of early death in HH patients.

Objectives

Iron is an essential nutrient, and its deficiency is worldwide an important cause of anaemia. Food and multivitamin fortification with iron is widely practised. This can have a deleterious effect in patients with hereditary hemochromatosis (HH), a frequent genetic disorder among Europeans. Normal amounts of dietary iron can lead to liver cirrhosis, diabetes, chronic arthritis, cardiomyopathy and liver cancer. Also heterozygotes (10% of all Europeans) are at risk, in particular for early cardio/cerebrovascular death. It is the objective to identify the mechanism of organ and vascular endothelium directed iron toxicity, to develop methods to measure toxic forms of iron in serum, to prevent these deleterious effects by identifying aggravating risk factors and designing iron chelators as safe food additives to scavenge toxic forms of iron.

(expected) Results and achievements

The results will entail elucidation of:

  • dietary, environmental and iron-related genetic risk factors for atherosclerosis and liver damage;
  • a rapid, inexpensive method for measurement of toxic iron;
  • design of oral iron chelators for prevention of iron damage;
  • mechanisms of iron toxicity on liver, heart and endothelium;
  • molecular mechanism of iron absorption in HH;
  • offer advice to industry and nutritionists for prevention of iron damage in the population at risk.

Partners

Universiteit of Rennes 1
Unité Inserm U-522
Faculté de Medecine - Chru Pontchaillou
Rue Henri le Guilloux, 2
35033 Rennes Cedex
France
The Hebrew Universiteit of Jerusalem
Department of Biological Chemistry
The Institute of Life Sciences
Givat Ram Campus
91904 Jerusalem
Israel
King's College London
Department of Pharmacy
Franklin-Wilkins Building
150 Stamford Street
SE1 8WA London
United Kingdom
King's College London
Department of Molecular Medicine
Rayne Institute
123 Coldharbour Lane
SE5 9NU London
United Kingdom
University of Modena and Reggio Emilia
Unit for the Study of Disorders of Iron Metabolism
Department of Internal Medicine
Policlinico, Via Del Pozzo 71
41100 Modena
Italy
ETH Zürich
Laboratorium für Anorganische Chemie
Universitätsstrasse 6
8092 Zürich
Switzerland


Fifth Framework Programme

PDF Version

:

Volume 1 (PDF 2.9 MB)

   

Volume 2 (PDF 1.9 MB)

 

Last update

:

23-09-2003



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