• Brigitte Sturm, Melissa Helminger, Hannes Steinkellner, Mohammad Mehdi Heidari, Hans Goldenberg, and Barbara Scheiber-Mojdehkar.
• Medical University of Vienna, Vienna, Austria.
• Eur. J. Clin. Invest. 2010 Jun 1; 40 (6): 561565561-5.

BackgroundFriedreich's ataxia (FRDA) is a neurodegenerative disorder caused by decreased expression of the mitochondrial protein frataxin. Recently we showed in a clinical pilot study in Friedreich's ataxia patients that recombinant human erythropoietin (rhuEPO) significantly increases frataxin-expression. In this in vitro study, we investigated the role of the erythropoietin receptor (EPO-R) in the frataxin increasing effect of rhuEPO and if nonerythropoietic carbamylated erythropoietin (CEPO), which cannot bind to the classical EPO-R increases frataxin expression.Materials And MethodsIn our experiments human erythroleukaemic K562 cells (+ EPO-R), human monocytic leukemia THP-1 cells (- EPO-R) and isolated primary lymphocytes from healthy control and FRDA patients were incubated with different concentrations of rhuEPO or CEPO. Frataxin-expression was detected by an electrochemical luminescence immunoassay (based on the principle of an ELISA).ResultsWe show that rhuEPO increases frataxin-expression in K562 cells (expressing EPO-R) as well as in THP-1 cells (without EPO-R expression). These results were confirmed by the finding that CEPO, which cannot bind to the classical EPO-R increased frataxin expression in the same concentration range as rhuEPO. In addition, we show that both EPO derivatives significantly increase frataxin-expression in vitro in control and Friedreich's ataxia patients primary lymphocytes.ConclusionOur results provide a scientific basis for further studies examining the effectiveness of nonerythropoietic derivatives of erythropoietin for the treatment of Friedreich's ataxia patients.

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