Idebenone and reduced cardiac hypertrophy in Friedreich's
ataxia.
Hausse AO, Aggoun Y, Bonnet D,
Sidi D, Munnich A, Rotig A, Rustin P.
Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, 149 rue de
Sevres, Paris, France.
Heart 2002 Apr;87(4):346-9
ABSTRACT
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.
DESIGN: Prospective, open trial.
SETTING: 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.
