Literature DB >> 12069112

Heart hypertrophy and function are improved by idebenone in Friedreich's ataxia.

Pierre Rustin1, Agnès Rötig, Arnold Munnich, Daniel Sidi.   

Abstract

Friedreich's ataxia (FRDA) is a neuro-degenerative disease causing limb and gait ataxia and hypertrophic cardiomyopathy. It results from a triplet expansion in the first intron of the frataxin gene encoding a mitochondrial protein of yet unknown function. Cells with low frataxin content display generalized deficiency of mitochondrial iron-sulfur cluster-containing proteins, which presumably denotes overproduction of superoxide radicals in these organelles. Idebenone, a short-chain quinone, may act as a potent free radical scavenger protecting mitochondria against oxidative stress. We therefore carried out an open trial of idebenone (oral supplementation; 5mg/kg/day) in a large series of FRDA patients and followed their left ventricular mass and function. Consistent and definitive worsening being observed in the natural course of the disease and cardiac hypertrophy having no chance of spontaneous reversal and to be subject to a placebo effect, the patient's heart status before and after the treatment was used to unambiguously establish the effect of the drug. After six months, heart ultrasound revealed more than 20% reduction of left ventricular mass in about half of the patients (p < 0.001) and no significant change in the other half. Since any measurable reversion of this pathogenic trait is highly significant, this demonstrates the efficiency of idebenone in controlling heart hypertrophy in FRDA. Owing to the absence of side effects of the drug, idebenone (up to 15mg/kg/day) should be prescribed for FRDA patients continuously as early as possible.

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Year:  2002        PMID: 12069112     DOI: 10.1080/10715760290021333

Source DB:  PubMed          Journal:  Free Radic Res        ISSN: 1029-2470


  27 in total

Review 1.  Friedreich ataxia-update on pathogenesis and possible therapies.

Authors:  Max Voncken; Panos Ioannou; Martin B Delatycki
Journal:  Neurogenetics       Date:  2003-12-19       Impact factor: 2.660

Review 2.  Therapeutic approaches to spinal and bulbar muscular atrophy.

Authors:  Srikanth Ranganathan; Kenneth H Fischbeck
Journal:  Trends Pharmacol Sci       Date:  2010-09-20       Impact factor: 14.819

3.  Cardiomyopathy of Friedreich's ataxia: use of mouse models to understand human disease and guide therapeutic development.

Authors:  R Mark Payne; P Melanie Pride; Clifford M Babbey
Journal:  Pediatr Cardiol       Date:  2011-03-01       Impact factor: 1.655

Review 4.  Drug development for rare mitochondrial disorders.

Authors:  Orest Hurko
Journal:  Neurotherapeutics       Date:  2013-04       Impact factor: 7.620

5.  Exercise capacity and idebenone intervention in children and adolescents with Friedreich ataxia.

Authors:  Bart E Drinkard; Randall E Keyser; Scott M Paul; Ross Arena; Jonathan F Plehn; Jack A Yanovski; Nicholas A Di Prospero
Journal:  Arch Phys Med Rehabil       Date:  2010-07       Impact factor: 3.966

Review 6.  Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease.

Authors:  Hong Ye; Tracey A Rouault
Journal:  Biochemistry       Date:  2010-06-22       Impact factor: 3.162

7.  Flavin adenine dinucleotide rescues the phenotype of frataxin deficiency.

Authors:  Pilar Gonzalez-Cabo; Sheila Ros; Francesc Palau
Journal:  PLoS One       Date:  2010-01-25       Impact factor: 3.240

8.  Current and emerging treatment options in the management of Friedreich ataxia.

Authors:  Michelangelo Mancuso; Daniele Orsucci; Anna Choub; Gabriele Siciliano
Journal:  Neuropsychiatr Dis Treat       Date:  2010-09-07       Impact factor: 2.570

Review 9.  Clinical experience with high-dose idebenone in Friedreich ataxia.

Authors:  Jörg B Schulz; Nicholas A Di Prospero; Kenneth Fischbeck
Journal:  J Neurol       Date:  2009-03       Impact factor: 4.849

10.  Pharmacokinetic properties and metabolism of idebenone.

Authors:  Klaus Kutz; Jürgen Drewe; Pierre Vankan
Journal:  J Neurol       Date:  2009-03       Impact factor: 4.849

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