title: Effects of erythropoietin on frataxin levels and mitochondrial function in Friedreich ataxia--a dose-response trial.
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.
authors: Department of Neurology, Medical University Innsbruck, Anichstrasse 35, Innsbruck, Austria.
authors: Wolfgang
authors: W
authors: Nachbauer
authors: Sascha
authors: S
authors: Hering
authors: Markus
authors: M
authors: Seifert
authors: Hannes
authors: H
authors: Steinkellner
authors: Brigitte
authors: B
authors: Sturm
authors: Barbara
authors: B
authors: Scheiber-Mojdehkar
authors: Markus
authors: M
authors: Reindl
authors: Alexander
authors: A
authors: Strasak
authors: Werner
authors: W
authors: Poewe
authors: Guenter
authors: G
authors: Weiss
authors: Sylvia
authors: S
authors: Boesch
references: Mov Disord. 2011 Mar;26(4):739-42
references: 21506154
references: J Clin Pharmacol. 2004 Sep;44(9):991-1002
references: 15317827
references: Biochim Biophys Acta. 1999 Nov 10;1413(3):99-107
references: 10556622
references: N Engl J Med. 2005 Mar 10;352(10):1011-23
references: 15758012
references: Anal Biochem. 1982 Jan 1;119(1):185-93
references: 6803610
references: J Mol Med (Berl). 2004 Aug;82(8):510-29
references: 15175861
references: Trends Genet. 2008 Aug;24(8):398-407
references: 18606475
references: Ann Neurol. 2007 Nov;62(5):521-4
references: 17702040
references: Am J Med Genet. 1999 Nov 19;87(2):168-74
references: 10533031
references: Eur J Biochem. 1997 Oct 1;249(1):77-84
references: 9363756
references: Brain. 1981 Sep;104(3):589-620
references: 7272714
references: Curr Hematol Rep. 2003 Mar;2(2):116-21
references: 12901142
references: Neurology. 2006 Jun 13;66(11):1717-20
references: 16769946
references: Neurotherapeutics. 2009 Jan;6(1):108-27
references: 19110203
references: Mov Disord. 2009 Sep 15;24(12):1779-84
references: 19562766
references: Anal Chim Acta. 2010 Feb 5;659(1-2):129-32
references: 20103114
references: J Mol Med (Berl). 2010 Apr;88(4):323-9
references: 19997898
references: Eur J Clin Invest. 2005 Nov;35(11):711-7
references: 16269021
references: J Neurol Neurosurg Psychiatry. 2004 Jul;75(7):1061-3
references: 15201375
references: Mov Disord. 2008 Oct 15;23(13):1940-4
references: 18759345
references: Eur J Haematol. 2007 Mar;78(3):183-205
references: 17253966
references: Blood. 1997 Jan 15;89(2):680-7
references: 9002972
references: Semin Hematol. 1991 Jul;28(3 Suppl 3):2-7; discussion 7-8
references: 1891720
references: Science. 1996 Mar 8;271(5254):1423-7
references: 8596916
references: J Neurosci. 2006 Jan 25;26(4):1269-74
references: 16436614
references: Nat Genet. 1997 Oct;17(2):215-7
references: 9326946
references: Hum Mol Genet. 2009 Jan 1;18(1):1-11
references: 18815198
references: J Pediatr Orthop. 2008 Mar;28(2):234-8
references: 18388721