Review: Friedreich Ataxia and Erythropoietin

Abstract

Abstract:In vitro and in vivo studies have provided evidence for neuroprotective properties of Erythropoietin in neurodegenerative disorders. Although the magnitude of effect is still controversial, very recent findings point to neuronal protection in the central nervous system by Erythropoietins. Erythropoietin is a powerful growth factor which enhances cellular size and ultimatively increases the number of mitochondria. Friedreich Ataxia (FA), an inherited neurodegenerative disorder is caused by a loss of function mutation in the first intron on chromosome 9. FA patients therefore suffer a marked reduction of Frataxin, a mitochondrial protein which is involved in mitochondrial iron homeostasis and/or assembly of iron-sulfur (FeS) proteins and heme synthesis. Mitochondrial dysfunction results in a deleterious energy deficit especially in tissues highly dependent on oxidative phosphorylation such as neurons, muscle cells or pancreatic insular cells. Beneficial effects of recombinant human Erythropoietin (rhuEPO) may derive from an increase in Frataxin levels through currently unknown post-transcriptional and/or post-translational mechanisms. Moreover, additional effects via BDNF and through mitochondrial iron chelation may complete the spectrum of rhuEPOs actions in FA and may be part of its beneficial treatment effects. However, there are clear limitations to chronic rhuEPO treatment. Apart from hematopoietic side effects, tumor growth may be enhanced by rhuEPO application. In this review we provide an overview of studies using rhuEPO in FA and discuss potential beneficial effects of Erythropoietin in FA.

Hot Topic: [Potential therapeutic use of recombinant human erythropoietin (Guest Editor: Elisio Costa)]

“…In this special supplement of "The Open Drug Discovery Journal", four reviewers papers have been included; two of them on renal tissue effect of EPO [10,11], one on the application of EPO in neurodegenerative disorders [12] and another about the levels of EPO in cardiac resynchronisation patients [13]. Finally, this supplement include an original article [14] that intend to study the effect of rhEPO on inflammation, oxidative stress and renal function/renoprotection, by using a rat model of moderate renal failure.…”