Antioxidants and other pharmacological treatments for Friedreich ataxia

Mary Kearney, Richard W Orrell, Michael Fahey, Massimo Pandolfo
Cochrane Database of Systematic Reviews 2012 April 18, (4): CD007791

BACKGROUND: Friedreich ataxia is a rare inherited autosomal recessive neurological disorder, characterised initially by unsteadiness in standing and walking, slowly progressing to wheelchair dependency usually in the late teens or early twenties. It is associated with slurred speech, scoliosis and pes cavus. Heart abnormalities cause premature death in 60% to 80% of people with the disorder. There is no easily defined clinical or biochemical marker and no known treatment. This is the first update of a review published in 2009.

OBJECTIVES: To examine the efficacy of antioxidants and other pharmacological treatments for Friedreich ataxia.

SEARCH METHODS: We searched The Cochrane Neuromuscular Disease Group Specialized Register (11 July 2011), CENTRAL (2011, Issue 3), MEDLINE (January 1966 to July 2011), EMBASE (January 1980 to July 2011), AMED (January 1985 to July 2011), CINAHL Plus (January 1937 to July 2011), LILACS (January 1982 to July 2011), ORPHANET (1990 to July 2011), TRIP (1998 to July 2011) and PEDRO (October 1999 to July 2011).

SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of drug treatment in people with genetically confirmed Friedreich ataxia. The primary outcome was change in ataxia rating scale as measured by the International Co-operative Ataxia Rating Scale (ICARS) after 12 months. Secondary outcomes included change in left ventricular heart mass as measured by magnetic resonance imaging or echocardiography. We excluded trials of shorter duration than 12 months.

DATA COLLECTION AND ANALYSIS: Three authors selected the trials and two authors extracted data. We obtained missing data from the one RCT that met our inclusion criteria. We planned to collect adverse event data from included studies.

MAIN RESULTS: More than 10 studies used idebenone in the treatment of Friedreich ataxia but only one small RCT, with 29 participants, using the synthetic antioxidant idebenone 5 mg/kg, fulfilled the selection criteria for this review. Other RCTs were of insufficient duration. We identified no additional RCT when the searches were updated in 2011. In the included study, the primary outcome specified for this review, change in ICARS scale, did not reveal any significant differences with idebenone treatment compared to placebo. The secondary outcome of change in left ventricular heart mass index as measured by magnetic resonance spectroscopy was not assessed. The second secondary outcome, change in left ventricular mass as measured by echocardiography, did improve significantly; there was a 10.7% worsening after 12 months of treatment in the placebo group and a 5.6% improvement in the idebenone group. The mean difference was 16.37% (95% CI 95% 2% to 31%). There were no adverse events. We considered the included study at low risk of bias in five of the seven domains assessed. A larger trial using idebenone published an interm report in May 2010 stating that the study had failed to reach its primary endpoint, which was change in the ICARS scale.

AUTHORS' CONCLUSIONS: No RCT using idebenone or any other pharmacological treatment has shown significant benefit on neurological symptoms associated with Friedreich ataxia. Idebenone has shown a positive effect on left ventricular heart mass but the clinical relevance of this change was not assessed in the included study.

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