title: Long-term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia.
abstract: Friedreich ataxia is an autosomal recessive disease with no available therapy. Clinical trials with erythropoietin in Friedreich ataxia patients have yielded conflicting results, and the long-term effect of the drug remains unknown.
  
  
  
  We designed a double-blind, placebo-controlled, multicenter trial to test the efficacy of epoetin alfa on 56 patients with Friedreich ataxia. The primary endpoint of the study was the effect of epoetin alfa on peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test. Secondary endpoints were frataxin levels in peripheral blood mononuclear cells, improvement in echocardiography findings, vascular reactivity, neurological progression, upper limb dexterity, safety, and quality of life. Epoetin alfa or placebo (1:1 ratio) was administered subcutaneously at a dose of 1200 IU/Kg of body weight every 12 weeks for 48 weeks.
  
  
  
  A total of 56 patients were randomized; 27 completed the study in the active treatment group, and 26 completed the study in the placebo group[KG1]. VO2 max was not modified after treatment (0.01 [-0.04 to 0.05]; P = .749), as well as most of the secondary endpoint measures, including frataxin. The 9-hole peg test showed a significant amelioration in the treatment group (-17.24 sec. [-31.5 to -3.0]; P = .018). The treatment was safe and well tolerated.
  
  
  
  Although results are not in favor of an effect of epoetin alfa in Friedreich ataxia, this is the largest trial testing its effect. It is still possible that epoetin alfa may show some symptomatic effect on upper-limb performance. This study provides class I evidence that erythropoietin does not ameliorate VO2 max in patients with Friedreich ataxia. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Saccà
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Puorro
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Marsili
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Antenora
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pane
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnologies, University of Rome, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Casali
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnologies, University of Rome, Rome, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Marcotulli
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Defazio
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Liuzzi
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tatillo
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Donata Maria
authors.initials: DM
authors.lastname: Cambriglia
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Schiano di Cola
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Giuliani
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Guardasole
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Salzano
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruvolo
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: De Rosa
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cittadini
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.affiliation: Department of Neurosciences, Odontostomatological and Reproductive Sciences, University Federico II, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D000068817:Epoetin Alfa / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005621:Friedreich Ataxia / Q000188:drug therapy*; D006397:Hematinics / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care
chemical_list: D006397:Hematinics; D000068817:Epoetin Alfa
keywords: CPET; Friedreich ataxia; VO2 max; erythropoietin; frataxin; trial