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Novel methodologies for assessing pools of labile (toxic) iron in biological fluids: Biological and clinical (diagnostic and therapeutic) implications

Non-transferin-bound iron (NTBI) represents forms of loosely bound iron that appear in the plasma of iron overloaded patients. A major component of NTBI, LPI (labile plasma iron), is chelatable and redox active, namely potentially toxic as it can engage in the formation of oxidizing species that can compromise the components of body fluids and cells. LPI can permeate into cells in an uncontrolled manner and lead to iron overload of critical tissues such as heart and endocrine glands and be fatal if not treated (with chelators). We recognized NTBI-LPI as a clinical parameter with both diagnostic and therapeutic value as the target of iron chelation or phlebotomy in the therapy of iron overload diseases such as thalassemia and hemochromatosis. For that purpose we developed 2 high throughput methods for detecting fluorimetrically NTBI and LPI in clinical specimens using original concepts and approaches. FeRiskTM and FeRosTM have been implemented for surveillance of NTBI and LPI in sera, respectively. The patented methods have been adapted as kits which are in the final validation stages by Aferrix, Ltd., an Israeli based company which is presently providing world-wide services to clinics and pharmaceutical companies carrying out clinical studies with novel iron chelators.

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THE HEBREW UNIVERSITY OF JERUSALEM - THE AUTHORITY FOR RESEARCH AND DEVELOPMENT
Safra Givat Ram Campus, Alexander Silberman Institite of Life Sciences, Dept of Biological Chemistry
91904 JERUSALEM
Israel