Abstract
Background
Antioxidant therapy has been applied to Friedreich's ataxia patients. We assessed
the effect of idebenone treatment in patients with Friedreich's ataxia.
Methods
Design: open-label trial. Nine Friedreich's ataxia patients (age range 11 - 19 years)
were treated with idebenone (5 mg/kg/day). Patients were evaluated before the start
of the therapy and throughout one year of treatment by International Cooperative Ataxia
Rating Scales (ICARS) scores, neurophysiological investigations and echocardiographic
measurements. Serum idebenone concentrations were measured by HPLC with electrochemical
detection. The number of GAA repeats at the frataxin gene was analyzed by PCR.
Results
Serum idebenone concentrations ranged between 0.04 - 0.37 µmol/L. Significantly positive
correlation was observed between idebenone values and the percentage of difference
between the ICARS scores before and 12 months after the start of the therapy (r =
0.883; p = 0.002). Significant reduction was observed comparing the ICARS scores in
baseline conditions and after 3 months of treatment (p = 0.017). No differences were
observed in echocardiographic measurements after the start of the therapy.
Conclusions
Cerebellar improvement was notable in mild patients after the first 3 months of therapy.
Idebenone treatment at early stages of the disease seems to reduce the progression
of cerebellar manifestations. Further blind trials with a greater number of patients
and higher doses are needed to fully assess the therapeutic potential of idebenone
in Friedreich's ataxia.
Key words
Friedreich's Ataxia - Idebenone Treatment - Hypertrophic Cardiomyopathy - FRDA Gene
- GAA Trinucleotide Repeat
References
- 1
Artuch R, Colomé C, Vilaseca M A, Aracil A, Pineda M.
Monitoring of idebenone treatment in patients with Friedreich's ataxia by high-pressure
liquid chromatography with electrochemical detection.
J Neurosci Meth.
2002;
115
63-66
- 2
Campuzano V, Montermini L, Moltó M D, Pianese L, Cossée M, Cañizares J. et al .
Friedreich ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat
expansion.
Science.
1996;
271
1423-1427
- 3
Geoffroy G, Barbeau A, Breton G, Lemieux B, Aube M, Leger C. et al .
Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia.
Can J Neurol Sci.
1976;
3
279-286
- 4
Gillis J C, Benfield P, McTavish D.
Idebenone.
Drugs and Aging.
1994;
5
133-152
- 5
Harding A E.
Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis
of early diagnostic criteria and intrafamilial clustering of clinical features.
Brain.
1981;
104
589-620
- 6
Isnard R, Kalotka H, Durr A, Cossee M, Schmitt M, Pousset F. et al .
Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length
in Friedreich's ataxia.
Circulation.
1997;
95
2247-2249
- 7
Lodi R, Cooper J M, Bradley J L, Manners D, Styles P, Taylor D J. et al .
Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia.
Proc Natl Acad Sci USA.
1999;
96
11492-11495
- 8
Lodi R, Hart P E, Rajagopalan B, Taylor D J, Crilley J G, Bradley J L. et al .
Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in
patients with Friedreich's ataxia.
Ann Neurol.
2001;
49
590-596
- 9
Monrós E, Moltó M D, Martínez F, Cañizares J, Blanca J, Vílchez J J. et al .
Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA
trinucleotid repeat.
Am J Hum Genet.
1997;
61
101-110
- 10
Palau F.
Friedreich's ataxia and frataxin: molecular genetics, evolution and pathogenesis (Review).
Int J Mol Med.
2001;
7
581-589
- 11
Rötig A, Lonlay P D, Chretien D, Foury F, Koenig M, Sidi D. et al .
Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia.
Nature Genet.
1997;
17
215-217
- 12
Rustin P, Munnich A, Rötig A.
Quinone analogs prevent enzymes targeted in Friedreich ataxia from iron-induced injury
in vitro.
Biofactors.
1999;
9
247-251
- 13
Rustin P, von Kleist-Retzow J C, Chantrel-Groussard K, Sidi D, Munnich A, Rotig A.
Effect of idebenone on cardiomyopathy in Friedreich's ataxia: a preliminary study.
Lancet.
1999;
354
1300-1301
- 14
Schöls L, Vorgerd M, Schillings M, Skipka G, Zange J.
Idebenone in patients with Friedreich ataxia.
Neuroscience Letters.
2001;
306
169-172
- 15
Trouillas P, Takayanagi T, Hallett M, Currier R D, Subramony S H, Wessel K. et al
.
International cooperative ataxia rating scale for pharmacological assessment of the
cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation
of Neurology.
J Neurol Sci.
1997;
145
205-211
Rafael Artuch
Biochemistry Department, Hospital Sant Joan de Déu
Passeig Sant Joan de Déu, 2
08950 Esplugues, Barcelona
Spain
Email: rartuch@hsjdbcn.org
