Erythropoietin in Friedreich ataxia: No effect on frataxin in a randomized controlled trial§

Authors

  • Caterina Mariotti MD,

    Corresponding author
    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
    • Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria, 11, 20133 Milano, Italy
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  • Roberto Fancellu MD,

    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Serena Caldarazzo MSc,

    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Lorenzo Nanetti MD,

    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Daniela Di Bella MD,

    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Massimo Plumari MSc,

    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Giuseppe Lauria MD,

    1. Neuromuscular Disease Unit, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Maria D. Cappellini MD,

    1. Hematological Unit, Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
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  • Lorena Duca MSc,

    1. Hematological Unit, Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
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  • Alessandra Solari MD,

    1. Neuroepidemiology Unit, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan; Italy
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  • Franco Taroni MD

    1. SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS, Istituto Neurologico “Carlo Besta,” Milan, Italy
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  • Funding agencies: This study was supported by the Italian Agency for Pharmaceutics (Agenzia Italiana del Farmaco; AIFA grant FARM6H95MJ; to F.T.).

  • Relevant conflicts of interest/financial disclosures: Caterina Mariotti received research support from the E-RARE program (01GM0820, RISCA), and Lundbeck Pharmaceuticals (Trial LUAA24493). Roberto Fancellu received research support from EUROSCA grant (LSHM-CT-2004-503304), and AIFA grant (FARM6H95MJ, to F.T.). Serena Caldarazzo received research support from AIFA grant (FARM6H95MJ, to F.T.). Maria D. Cappellini received financial support from the CCM2010 grant on rare diseases (Italian Ministry of Health) and from Novartis Pharma (clinical trials on ICL670). Alessandra Solari received research support from the Fondazione Italiana Sclerosi Multipla (FISM; grants 2007/R/19; 2009/R/28), board membership fees from Novartis, and speaking honoraria from Sanofi Aventis. Franco Taroni received research support from AIFA (grant FARM6H95MJ) and ApoPharma (Study LA29-0207).

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Background:

Friedreich ataxia is a rare disease caused by GAA-trinucleotide-repeat expansions in the frataxin gene, leading to marked reduction of qualitatively normal frataxin protein. Recently, human recombinant erythropoietin was reported to increase frataxin levels in patients with Friedreich ataxia.

Methods:

We performed a 6-month, randomized placebo-controlled, double-blind, dose-response pilot trial to assess the safety and efficacy of erythropoietin in increasing frataxin levels. Sixteen adult patient with Friedreich ataxia were randomly assigned to erythropoietin (n = 11) or matching placebo (n = 5). All patients continued Idebenone treatment (5 mg/kg/day). Treatment consisted of a 6-month scaling-up phase, in which erythropoietin was administered intravenously at the following doses: 20,000 IU every 3 weeks, 40,000 IU every 3 weeks, and 40,000 IU every 2 weeks.

Results:

Erythropoietin treatment was safe and well tolerated, but did not result in any significant hematological, clinical, or biochemical effects in Friedreich ataxia patients. © 2012 Movement Disorder Society

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