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Effects of Erythropoietin on Frataxin Levels and Mitochondrial Function in Friedreich Ataxia – a Dose–Response Trial

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Abstract

Friedreich ataxia (FRDA) is an autosomal recessive inherited neurodegenerative disorder leading to reduced expression of the mitochondrial protein frataxin. Previous studies showed frataxin upregulation in FRDA following treatment with recombinant human erythropoietin (rhuEPO). Dose–response interactions between frataxin and rhuEPO have not been studied until to date. We administered escalating rhuEPO single doses (5,000, 10,000 and 30,000 IU) in monthly intervals to five adult FRDA patients. Measurements of frataxin, serum erythropoietin levels, iron metabolism and mitochondrial function were carried out. Clinical outcome was assessed using the “Scale for the assessment and rating of ataxia”. We found maximal erythropoietin serum concentrations 24 h after rhuEPO application which is comparable to healthy subjects. Frataxin levels increased significantly over 3 months, while ataxia rating did not reveal clinical improvement. All FRDA patients had considerable ferritin decrease. NADH/NAD ratio, an indicator of mitochondrial function, increased following rhuEPO treatment. In addition to frataxin upregulation in response to continuous low-dose rhuEPO application shown in previous studies, our results indicate for a long-lasting frataxin increase after single high-dose rhuEPO administration. To detect frataxin-derived neuroprotective effects resulting in clinically relevant improvement, well-designed studies with extended time frame are required.

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Acknowledgements

This study was supported by a grant of the Austrian National Bank (ÖNB, Jubiläumsfonds), Medical University Innsbruck, Tiroler Landeskrankenanstalten.

Conflicts of Interest

There is no conflict of interest in the work presented in this manuscript.

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Authors and Affiliations

  1. Department of Neurology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Wolfgang Nachbauer, Sascha Hering, Markus Reindl, Werner Poewe & Sylvia Boesch

  2. Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Markus Seifert & Guenter Weiss

  3. Department of Medical Chemistry, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria

    Hannes Steinkellner, Brigitte Sturm & Barbara Scheiber-Mojdehkar

  4. Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Schöpfstrasse 41, 6020, Innsbruck, Austria

    Alexander Strasak

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  1. Wolfgang Nachbauer
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  10. Guenter Weiss
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  11. Sylvia Boesch
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Correspondence to Sylvia Boesch.

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Nachbauer, W., Hering, S., Seifert, M. et al. Effects of Erythropoietin on Frataxin Levels and Mitochondrial Function in Friedreich Ataxia – a Dose–Response Trial. Cerebellum 10, 763–769 (2011). https://doi.org/10.1007/s12311-011-0287-9

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