Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia.
BACKGROUND
Friedreich's ataxia encodes a protein of unknown function, frataxin. The loss of frataxin is caused by a large GAA trinucleotide expansion in the first intron of the gene, resulting in deficiency of a Krebs cycle enzyme, aconitase, and of three mitochondrial respiratory chain complexes (I-III). This causes oxidative stress. Idebenone, a short chain quinone acting as an antioxidant, has been shown to protect heart muscle against oxidative stress in some patients.


OBJECTIVE
To assess the efficiency of idebenone on cardiac hypertrophy in Friedreich's ataxia.


METHODS
Prospective, open trial.


METHODS
Tertiary care centre.


METHODS
Idebenone (5 mg/kg/day) was given orally to 38 patients with Friedreich's ataxia aged 4-22 years (20 males, 18 females). Cardiac ultrasound indices were recorded before and after idebenone treatment.


RESULTS
After six months, cardiac ultrasound indicated a reduction in left ventricular mass of more than 20% in about half the patients (p < 0.001). The shortening fraction was initially reduced in six of the 38 patients (by between 11-26%) and it improved in five of these. In one patient, the shortening fraction only responded to 10 mg/kg/day of idebenone. No correlation was found between responsiveness to idebenone and age, sex, initial ultrasound indices, or the number of GAA repeats in the frataxin gene.


CONCLUSIONS
Idebenone is effective at controlling cardiac hypertrophy in Friedreich's ataxia. As the drug has no serious side effects, there is a good case for giving it continuously in a dose of 5-10 mg/kg/day in patients with Friedreich's ataxia at the onset of hypertrophic cardiomyopathy.
Hausse
A O
AO
Service de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de Sévres, Paris, France.
Aggoun
Y
Y
Bonnet
D
D
Sidi
D
D
Munnich
A
A
Rötig
A
A
Rustin
P
P
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D016227:Benzoquinones / Q000008:administration & dosage*; D006332:Cardiomegaly / Q000503:physiopathology / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005621:Friedreich Ataxia / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome; D014451:Ubiquinone / Q000031:analogs & derivatives; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D000975:Antioxidants; D016227:Benzoquinones; D014451:Ubiquinone; C036619:idebenone