Neurological Disorders Associated with Iron Misdistribution: The Therapeutic Potential of Siderophores

Or Kakhlon, Bill Breuer, Arnold Munnich, Z. Ioav Cabantchik

    Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


    The association between iron accumulation and oxidative cell damage in specific regions of the brain has raised the possibility of using iron chelation as a therapeutic strategy in neurodegenerative disorders. In this review, Friedreich’s ataxia (FRDA) is described as a paradigm of a disorder in which cell damage is associated with misdistribution of cell iron resulting from aberrant utilization of the metal by mitochondria. Frataxin-deficient cells, serving as an in vitro model of FRDA, were used as a model for testing the effects of a chelator with the ability to sequester cell iron as well as to donate it to biological acceptors inside or outside cells (termed here a siderophore). The clinically used siderophore deferiprone (DFP) was shown to reduce mitochondrial labile iron accumulation and restore cell functions affected by frataxin deficiency. In a translation of these findings to the clinical setting, moderate doses of DFP were administered to selected patients with FRDA or neurodegeneration with brain iron accumulation (NBIA) as part of open-label studies. Treatment with DFP resulted in a significant reduction in foci of brain iron accumulation and in some functional improvements, with only minor changes in body iron stores. The prospects of using drug-mediated iron relocation vs. chelation are critically discussed in relation to other neurodegenerative disorders in which accumulated (toxic) iron has been implicated as a causative factor in regional oxidative damage, such as Parkinson’s disease or Alzheimer’s disease.
    Original languageAmerican English
    Title of host publicationOxidative Stress and Free Radical Damage in Neurology
    EditorsNatan Gadoth, Hans Hilmar Göbel
    Place of PublicationTotowa, NJ
    PublisherHumana Press
    Number of pages22
    ISBN (Print)978-1-60327-514-9
    StatePublished - 2011


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