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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 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 Citation Map 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 Red Cells Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Selective iron chelation in Friedreich ataxia: biologic and clinical implications Nathalie Boddaert1, Kim Hanh Le Quan Sang2, Agnès Rötig2, Anne Leroy-Willig3, Serge Gallet4, Francis Brunelle1, Daniel Sidi5, Jean-Christophe Thalabard2, Arnold Munnich2, and Z. Ioav Cabantchik6 1 Pediatric Radiology Unit and 2 Medical Genetic Clinic and Research Unit, Institut National de la Santé et de la Recherche Médicale (INSERM) 781, Hôpital Necker-Enfants Malades and Université Paris V René Descartes, Paris, France; 3 U2R2M, Centre national de la recherche scientifique (CNRS) UMR 8081, Université Paris Sud, Orsay, France; 4 Pediatric Unit, Hôpital de Montluçon, Montluçon, France; 5 Pediatric Cardiology Unit, Hôpital Necker-Enfants Malades and Université Paris V René Descartes, Paris, France; 6 Institute of Life Sciences and Charles E. Smith Laboratory of Psychobiology, Hebrew University, Givat Ram, Jerusalem, Israel Genetic disorders of iron metabolism and chronic inflammation often evoke local iron accumulation. In Friedreich ataxia, decreased iron-sulphur cluster and heme formation leads to mitochondrial iron accumulation and ensuing oxidative damage that primarily affects sensory neurons, the 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 magnetic resonance imaging (MRI) of Friedreich ataxia patients compared with age-matched controls revealed smaller and irregularly shaped dentate nuclei with significantly (P < .027) higher H-relaxation rates R2*, indicating regional iron accumulation. A 6-month treatment with 20 to 30 mg/kg/d deferiprone of 9 adolescent patients with no overt cardiomyopathy reduced R2* from 18.3 s–1 (± 1.6 s–1) to 15.7 s–1 (± 0.7 s–1; P < .002), specifically in dentate nuclei and proportionally to the initial R2* (r = 0.90). Chelator treatment caused no apparent hematologic or neurologic 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 hematologic 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: 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] 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, June 30, 2009; (2009) awp152v1. [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. Cabantchik Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation Blood, December 15, 2008; 112(13): 5219 - 5227. [Abstract] [Full Text] [PDF] K. Li, E. K. Besse, D. Ha, G. Kovtunovych, and T. A. Rouault Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia Hum. Mol. Genet., August 1, 2008; 17(15): 2265 - 2273. [Abstract] [Full Text] [PDF] M. Whitnall, Y. S. Rahmanto, R. Sutak, X. Xu, E. M. Becker, M. R. Mikhael, P. Ponka, and D. R. Richardson The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation PNAS, July 15, 2008; 105(28): 9757 - 9762. [Abstract] [Full Text] [PDF] C. K. Lim, D. S. Kalinowski, and D. R. 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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