Erythropoietin in Friedreich ataxia

Caterina Mariotti, Wolfgang Nachbauer, Marta Panzeri, Werner Poewe, Franco Taroni, Sylvia Boesch

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

In Friedreich ataxia (FRDA), several candidate substances including erythropoietin (EPO) focus on increase in the amount of frataxin and aim to counteract the consequences of frataxin deficiency. Evidence for recombinant human erythropoietin (rHuEPO) in FRDA is based on in vitro studies using mouse neuronal cell lines, human fibroblasts, cardiomyocytes, and primary lymphocytes from FRDA patients or control subjects which showed a dose-dependent increase of frataxin after incubation with different erythropoietins. The mechanism by which EPO induces frataxin increase remains to be elucidated, but may involve post-transcriptional and/or post-translational modifications of frataxin or alterations in frataxin half-life and metabolism. In vivo data on rHuEPO's ability to increase frataxin in FRDA patients is contradictory as studies on the effect of EPO derivatives in FRDA differ in treatment regimen, sample size, and duration. Open-label studies indicate for sustained frataxin increase, decrease of oxidative stress, and clinical improvement in FRDA patients after administration of rHuEPO. Two randomized controlled studies found acceptable safety and tolerability of EPO derivatives in FRDA. Secondary outcome measures, however, such as frataxin up-regulation and clinical efficacy were not met. This review will focus on (i) pre-clinical work on erythropoietins in FRDA and (ii) clinical studies in FRDA patients exposed to erythropoietins.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalJournal of Neurochemistry
Volume126
Issue numberSUPPL.1
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Friedreich Ataxia
Erythropoietin
Derivatives
frataxin
Oxidative stress
Lymphocytes
Fibroblasts
Post Translational Protein Processing
Cardiac Myocytes
Metabolism
Sample Size
Half-Life
Labels
Oxidative Stress
Up-Regulation
Cells
Outcome Assessment (Health Care)
Safety
Cell Line

Keywords

  • erythropoietin
  • Friedreich ataxia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Mariotti, C., Nachbauer, W., Panzeri, M., Poewe, W., Taroni, F., & Boesch, S. (2013). Erythropoietin in Friedreich ataxia. Journal of Neurochemistry, 126(SUPPL.1), 80-87. https://doi.org/10.1111/jnc.12301

Erythropoietin in Friedreich ataxia. / Mariotti, Caterina; Nachbauer, Wolfgang; Panzeri, Marta; Poewe, Werner; Taroni, Franco; Boesch, Sylvia.

In: Journal of Neurochemistry, Vol. 126, No. SUPPL.1, 08.2013, p. 80-87.

Research output: Contribution to journalArticle

Mariotti, C, Nachbauer, W, Panzeri, M, Poewe, W, Taroni, F & Boesch, S 2013, 'Erythropoietin in Friedreich ataxia', Journal of Neurochemistry, vol. 126, no. SUPPL.1, pp. 80-87. https://doi.org/10.1111/jnc.12301
Mariotti C, Nachbauer W, Panzeri M, Poewe W, Taroni F, Boesch S. Erythropoietin in Friedreich ataxia. Journal of Neurochemistry. 2013 Aug;126(SUPPL.1):80-87. https://doi.org/10.1111/jnc.12301
Mariotti, Caterina ; Nachbauer, Wolfgang ; Panzeri, Marta ; Poewe, Werner ; Taroni, Franco ; Boesch, Sylvia. / Erythropoietin in Friedreich ataxia. In: Journal of Neurochemistry. 2013 ; Vol. 126, No. SUPPL.1. pp. 80-87.
@article{8d0ddeac6dfd4366bac29e897815f1fe,
title = "Erythropoietin in Friedreich ataxia",
abstract = "In Friedreich ataxia (FRDA), several candidate substances including erythropoietin (EPO) focus on increase in the amount of frataxin and aim to counteract the consequences of frataxin deficiency. Evidence for recombinant human erythropoietin (rHuEPO) in FRDA is based on in vitro studies using mouse neuronal cell lines, human fibroblasts, cardiomyocytes, and primary lymphocytes from FRDA patients or control subjects which showed a dose-dependent increase of frataxin after incubation with different erythropoietins. The mechanism by which EPO induces frataxin increase remains to be elucidated, but may involve post-transcriptional and/or post-translational modifications of frataxin or alterations in frataxin half-life and metabolism. In vivo data on rHuEPO's ability to increase frataxin in FRDA patients is contradictory as studies on the effect of EPO derivatives in FRDA differ in treatment regimen, sample size, and duration. Open-label studies indicate for sustained frataxin increase, decrease of oxidative stress, and clinical improvement in FRDA patients after administration of rHuEPO. Two randomized controlled studies found acceptable safety and tolerability of EPO derivatives in FRDA. Secondary outcome measures, however, such as frataxin up-regulation and clinical efficacy were not met. This review will focus on (i) pre-clinical work on erythropoietins in FRDA and (ii) clinical studies in FRDA patients exposed to erythropoietins.",
keywords = "erythropoietin, Friedreich ataxia",
author = "Caterina Mariotti and Wolfgang Nachbauer and Marta Panzeri and Werner Poewe and Franco Taroni and Sylvia Boesch",
year = "2013",
month = "8",
doi = "10.1111/jnc.12301",
language = "English",
volume = "126",
pages = "80--87",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "SUPPL.1",

}

TY - JOUR

T1 - Erythropoietin in Friedreich ataxia

AU - Mariotti, Caterina

AU - Nachbauer, Wolfgang

AU - Panzeri, Marta

AU - Poewe, Werner

AU - Taroni, Franco

AU - Boesch, Sylvia

PY - 2013/8

Y1 - 2013/8

N2 - In Friedreich ataxia (FRDA), several candidate substances including erythropoietin (EPO) focus on increase in the amount of frataxin and aim to counteract the consequences of frataxin deficiency. Evidence for recombinant human erythropoietin (rHuEPO) in FRDA is based on in vitro studies using mouse neuronal cell lines, human fibroblasts, cardiomyocytes, and primary lymphocytes from FRDA patients or control subjects which showed a dose-dependent increase of frataxin after incubation with different erythropoietins. The mechanism by which EPO induces frataxin increase remains to be elucidated, but may involve post-transcriptional and/or post-translational modifications of frataxin or alterations in frataxin half-life and metabolism. In vivo data on rHuEPO's ability to increase frataxin in FRDA patients is contradictory as studies on the effect of EPO derivatives in FRDA differ in treatment regimen, sample size, and duration. Open-label studies indicate for sustained frataxin increase, decrease of oxidative stress, and clinical improvement in FRDA patients after administration of rHuEPO. Two randomized controlled studies found acceptable safety and tolerability of EPO derivatives in FRDA. Secondary outcome measures, however, such as frataxin up-regulation and clinical efficacy were not met. This review will focus on (i) pre-clinical work on erythropoietins in FRDA and (ii) clinical studies in FRDA patients exposed to erythropoietins.

AB - In Friedreich ataxia (FRDA), several candidate substances including erythropoietin (EPO) focus on increase in the amount of frataxin and aim to counteract the consequences of frataxin deficiency. Evidence for recombinant human erythropoietin (rHuEPO) in FRDA is based on in vitro studies using mouse neuronal cell lines, human fibroblasts, cardiomyocytes, and primary lymphocytes from FRDA patients or control subjects which showed a dose-dependent increase of frataxin after incubation with different erythropoietins. The mechanism by which EPO induces frataxin increase remains to be elucidated, but may involve post-transcriptional and/or post-translational modifications of frataxin or alterations in frataxin half-life and metabolism. In vivo data on rHuEPO's ability to increase frataxin in FRDA patients is contradictory as studies on the effect of EPO derivatives in FRDA differ in treatment regimen, sample size, and duration. Open-label studies indicate for sustained frataxin increase, decrease of oxidative stress, and clinical improvement in FRDA patients after administration of rHuEPO. Two randomized controlled studies found acceptable safety and tolerability of EPO derivatives in FRDA. Secondary outcome measures, however, such as frataxin up-regulation and clinical efficacy were not met. This review will focus on (i) pre-clinical work on erythropoietins in FRDA and (ii) clinical studies in FRDA patients exposed to erythropoietins.

KW - erythropoietin

KW - Friedreich ataxia

UR - http://www.scopus.com/inward/record.url?scp=84880388935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880388935&partnerID=8YFLogxK

U2 - 10.1111/jnc.12301

DO - 10.1111/jnc.12301

M3 - Article

C2 - 23859343

AN - SCOPUS:84880388935

VL - 126

SP - 80

EP - 87

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - SUPPL.1

ER -