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Idebenone in Friedreich ataxia and Leber’s hereditary optic neuropathy: close mechanisms, similar therapy?: Table 1

2016; Oxford University Press; Volume: 139; Issue: 7 Linguagem: Inglês

10.1093/brain/aww085

1460-2156

Manuel Schiff, Pierre Rustin,

Endoplasmic Reticulum Stress and Disease

Sir, In 1999, we reported in a preliminary study that idebenone (Mnesis) decreased heart hypertrophy in three young patients with Friedreich ataxia, possibly with slight improvement in delicate movements (Rustin et al. , 1999 b ). In the vast majority of patients with Friedreich ataxia, an abnormal GAA expansion is found in the first intron of the frataxin ( FXN ) gene impairing transcription of the gene (Campuzano et al. , 1996). The resulting loss of function of the mitochondria-targeted frataxin protein leads to a deficiency of the mitochondrial iron-sulphur containing proteins (ISP), including complexes I, II and III of the respiratory chain in the heart of the patients (Rotig et al. , 1997). Defect of the ISP was shown to cause an iron-dependent oxidative stress which could be controlled in vitro by reduced idebenone (Rustin et al. , 1999 a ). In vivo , idebenone can be reduced by respiratory chain and/or NQO1 (NADH quinone oxidoreductase) activity (Haefeli et al. , 2011). Following the preliminary report of idebenone efficacy to counteract …