Background
Friedreich’s ataxia (FA), the most common form of degenerative ataxia, is thought to be caused by respiratory chain deficiency, with mitochondrial iron accumulation and oxidative stress. Idebenone, a free-radical scavenger, protects mitochondrial function in in vitro FA models. A recent study has reported improvement of FA-associated cardiomyopathy with idebenone, but its effect on neurological dysfunctions remains unknown.

Purpose
To collect clinical and biochemical data in order to measure neurological effect of idebenone.

Methods
19 FA patients (mean age 33.6 years, range 13 to 68) agreed to take idebenone and were prospectively followed. The international cooperative ataxia rating scale (ICARS) was used to quantify ataxia. Blood samples were collected to measure malondialdehyde (MDA) levels, a product of lipid peroxydation.

Results

• Idebenone was taken by 14 patients at 5 mg/kg and by 5 patients at 10 mg/kg
• 15/19 (79%) reported improvement: - dysarthria:12 cases (63%) - hand skillness: 4 cases (21%) - handwriting: 7 cases (37%) (Fig. 1) - fatigue: 9 cases (47%).
• Improvement appeared after a few month in 12 cases, but faster in 3 patients
• In 3 patients idebenone was stopped and a worsening in ataxia was observed.
• There were no side effects related to the treatment.

Results (cnt) • MDA has been measured in whole blood on EDTA, and levels were increased in FA patients treated with idebenone, compared with those without treatment (p= 0.04) (Fig. 2)	Fig. 2 MDA level with and without idebenone
• There was a clear increase of MDA levels after introduction of treatment with idebenone (Fig. 3).	Fig3 MDAlevels in three FA patients before and after treatment with idebenone

Conclusions

• Although not controlled, this trial suggests that idebenone may improve cerebellar ataxia in FA patients
  
  
• The whole blood MDA results obtained in this study suggests that idebenone may be efficient by an action on respiratory chain that is different from a decrease in oxydative stress
  
  
• MDA or other molecules could be used in future studies to monitor treatments