Expanding view of phenotype and oxidative stress in Friedreich's ataxia patients with and without idebenone

摘要: Friedreich's ataxia (FRDA), the most common autosomal recessive ataxia, is characterised by progressive with dysarthria of speech, loss deep-tendon reflexes, impaired vibratory and proprioceptive sensations corticospinal weakness a Babinski's sign. Patients eventually also develop kyphoscoliosis, cardiomyopathy diabetes mellitus. The disease GAA repeat disorder resulting in severely reduced levels frataxin, secondary increased sensitivity to oxidative stress. anti-oxidative drug, idebenone, effective against FRDA-associated cardiomyopathy. We provide detailed clinical, electrophysiological biochemical data from 20 genetically confirmed FRDA patients have analysed relationship between phenotype, genotype malondialdehyde (MDA), which marker superoxide formation. assessed effects idebenone biochemically measuring blood MDA clinically serial measurements International Cooperative Ataxia Rating Scale (ICARS). length influenced age at onset (p <0.001), severity = 0.02), presence 0.04) low-frequency hearing 0.009). Multilinear regression analysis showed 0.006) that ICARS was dependent on two variables duration 0.01) size expansion 0.02). found no correlation bilateral palpebral ptosis, visual impairment, mellitus or skeletal deformities, all appear be signs progression rather than severity. discuss more thoroughly underrecognised clinical findings: ptosis length-dependent loss. average remained unchanged 10 for whom follow-up treatment available (mean 2.9 years), whereas treated reported an improvement (63%), hand dexterity (58%) fatigue (47%) after taking drug several weeks months. Oxidative stress unexpected increase 0.04), we putative underlying mechanism this result, could then explain unique efficacy treating cardiomyopathy, as opposed other antioxidative drugs. Indeed, not only powerful stimulator complexes II III respiratory chain, but inhibitor complex I activity, promoting Our preliminary observations are first date supporting effect delaying neurological worsening. results point dual need controlled studies assess its potential toxicity high doses one hand, revisit exact mechanisms physiopathology while recent reports suggest non-oxidative pathophysiology disease.