Bioenergetics of the Calf Muscle in Friedreich Ataxia
Patients Measured by 31P-MRS Before and After
Treatment with Recombinant Human Erythropoietin
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.
EU Clinical Trials Register 2008-000040-13
Nachbauer W, Boesch S, Schneider R, Eigentler A, Wanschitz J, et al. (2013) Bioenergetics of the Calf Muscle in Friedreich Ataxia Patients Measured by
31P-MRS Before and After Treatment with Recombinant Human Erythropoietin. PLoS ONE 8(7): e69229. doi:10.1371/journal.pone.0069229
Annalisa Pastore, National Institute for Medical Research, Medical Research Council, London, United Kingdom
March 5, 2013; Accepted June 6, 2013; Published July 29, 2013
2013 Nachbauer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study was funded by a grant of the Austrian National Bank (‘‘O¨ NB Jubila¨umsfond 12948’’). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
This study was funded by a research grant of the Austrian National Bank (‘‘O¨ NB Jubila¨umsfond 12948’’). This grant does not alter the
authors’ adherence to all the PLOS ONE policies on sharing data and materials.
1, Sylvia Boesch1*, Rainer Schneider2, Andreas Eigentler1, Julia Wanschitz1,
1, Michael Schocke3
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria, 2 Department of Biochemistry, Leopold-Franzens-University Innsbruck, Innsbruck, Austria,
Department of Radiology, Medical University Innsbruck, Innsbruck, Austria
shared by Juan Carlos Baiges