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Clinical Trial
. 2013 Jul 29;8(7):e69229.
doi: 10.1371/journal.pone.0069229. Print 2013.

Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin

Wolfgang Nachbauer  1 , Sylvia Boesch, Rainer Schneider, Andreas Eigentler, Julia Wanschitz, Werner Poewe, Michael Schocke
Affiliations
Clinical Trial

Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin

Wolfgang Nachbauer et al. PLoS One. .

Abstract

Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO) is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS). Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr) depletion and increased accumulation of inorganic phosphate (Pi) during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.

Trial registration: EU Clinical Trials Register2008-000040-13.

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Conflict of interest statement

Competing Interests: This study was funded by a research grant of the Austrian National Bank (“ÖNB Jubiläumsfond 12948”). This grant does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. CONSORT Flow Diagram.
Figure 2
Figure 2. Phosphocreatine and inorganic phosphate kinetics.
Time course of phosphocreatine (PCr) and inorganic phosphate (Pi) are shown during exercise in increment 1 and recovery period after maximal exhaustive exercise. Curves are shown as a comparison of healthy controls (dashed curves) to treatment naïve FRDA patients at baseline (solid curves) and FRDA patients after rhuEPO administration (dotted curves). Values are given as a function of time (x) in percentage of changes in PCr and Pi from baseline of the respective increment (100%) and are based on the asymptotic exponential regression model formula image
Figure 3
Figure 3. Time constants of phosphocreatine and inorganic phosphate.
PCr and Pi time constants (t) and steady state levels (SS) are given during exercise and recovery as a comparison of FRDA patients before (FRDA baseline) and after (FRDA rhuEPO) erythropoietin stimulation to healthy control subjects. Values are shown as mean and standard deviation. For absolute values compare table 2 .
See this image and copyright information in PMC

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