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Blood, 1 July 2007, Vol. 110, No. 1, pp. 401-408. Prepublished online as a Blood First Edition Paper on March 22, 2007; DOI 10.1182/blood-2006-12-065433. This Article Full Text (PDF) All Versions of this Article: blood-2006-12-065433v1 110/1/401    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Boddaert, N. Articles by Cabantchik, Z. I. Search for Related Content PubMed PubMed Citation Articles by Boddaert, N. Articles by Cabantchik, Z. I. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 27, 2006 Accepted March 14, 2007 Selective iron chelation in Friedreich ataxia. Biological and clinical implications Nathalie Boddaert, Kim Hanh Le Quan Sang, Agnes Rotig, Anne Leroy-Willig, Serge Gallet, Francis Brunelle, Daniel Sidi, Jean-Christophe Thalabard, Arnold Munnich, and Zvi Ioav Cabantchik* Pediatric Radiology Unit, ERM0205, Hopital Necker-Enfants Malades & Universite Paris V Rene Descartes, Paris, France Medical Genetic Clinic and Research Unit INSERM 781, Hopital Necker-Enfants Malades & Universite Paris V Rene Descartes, Paris, France U2R2M, CNRS UMR 8081, Universite Paris Sud, Orsay, France Pediatric Unit, Hopital de Montlucon, Montlucon, France Pediatric Cardiology Unit, Hopital Necker-Enfants Malades & Universite Paris V Rene Descartes, Paris, France Institute of Life Sciences, and Charles E. Smith Laboratory of Psychobiology, Hebrew University of Jerusalem, Jerusalem, Israel * Corresponding author; email: ioav{at}cc.huji.ac.il. Genetic disorders of iron metabolism and chronic inflammation often evoke local iron accumulation. In Friedreich-ataxia, decreased iron-sulphur-cluster and haem formation leads to mitochondrial iron accumulation and ensuing oxidative damage that affect primarily sensory neurons, myocardium and endocrine glands. We assessed the possibility of reducing brain iron accumulation in Friedreich-ataxia patients with a membrane-permeant chelator capable of shuttling chelated-iron from cells to transferrin, using regimens suitable for patients with no systemic iron overload. Brain MRI of Friedreich-ataxia patients compared to age-matched controls revealed smaller and irregularly shaped dentate-nuclei with significantly (p<0.027) higher H-relaxation rates R2*, indicating regional iron accumulation. A six-month treatment with 20-30mg/kg/d deferiprone applied on 11/20 adolescent patients with no overt cardiomyopathy reduced R2* from 18.3±1.6 to 15.7±0.7msec-1 (p<0.002) specifically in dentate nuclei and proportionally to the initial R2* (r=0.90). Chelator-treatment caused no apparent haematological or neurological side-effects, while reducing neuropathy and ataxic-gait in the youngest patients. To our knowledge, this is the first clinical demonstration of chelation removing labile iron accumulated in a specific brain area implicated in a neurodegenerative disease. The use of moderate chelation for relocating iron from areas of deposition to areas of deprivation has clinical implications for various neurodegenerative and haematological disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ironing out a therapy for Friedreich ataxia Grazia Isaya Blood 2007 110: 1-2. [Full Text] [PDF] This article has been cited by other articles: G. Kollberg, M. Tulinius, A. Melberg, N. Darin, O. Andersen, D. Holmgren, A. Oldfors, and E. Holme Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy Brain, August 1, 2009; 132(8): 2170 - 2179. [Abstract] [Full Text] [PDF] D. Aquino, A. Bizzi, M. Grisoli, B. Garavaglia, M. G. Bruzzone, N. Nardocci, M. Savoiardo, and L. Chiapparini Age-related Iron Deposition in the Basal Ganglia: Quantitative Analysis in Healthy Subjects Radiology, July 1, 2009; 252(1): 165 - 172. [Abstract] [Full Text] [PDF] A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF] O. Kakhlon, H. Manning, W. Breuer, N. Melamed-Book, C. Lu, G. Cortopassi, A. Munnich, and Z. I. 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Richardson Protection against Hydrogen Peroxide-Mediated Cytotoxicity in Friedreich's Ataxia Fibroblasts Using Novel Iron Chelators of the 2-Pyridylcarboxaldehyde Isonicotinoyl Hydrazone Class Mol. Pharmacol., July 1, 2008; 74(1): 225 - 235. [Abstract] [Full Text] [PDF] Y.-S. Sohn, W. Breuer, A. Munnich, and Z. I. Cabantchik Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications Blood, February 1, 2008; 111(3): 1690 - 1699. [Abstract] [Full Text] [PDF]

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