A new integrated biochemical approach shows a dec rease of oxidative stress in idebenone.-treated FRDA patients after oral tocotrienol supplementation

Friedreich’s Ataxia (FRDA) is characterized by oxidative stress as well as by impaired mitochondrial functions. Patients are currently treated with idebenone, a CoQ10 analogue, and the therapeutic efficacy of Vit. E has been documented. In order to develop a model useful to investigate the efficacy of the approaches for oxidative stress damage protection, a number of biochemical parameters related to oxidative stress were identified and studied in blood samples from five young FRDA patients who assumed tocotrienol (5 mg/kg/day), a highly lipophilic Vit. E analogue, for two months. The following features were studied: white blood cell gene expression of SOD-1, SOD-2, catalase, GPX-1, GSR and GSTM-1; plasma content of GSH and GSSG; plasma Oxygen Radical Absorbance Capacity; amount of plasma carbonylated proteins; lipid composition of erythrocyte membranes. Such wide array of different markers consistently pointed to the presence of oxidative stress in FRDA patients, despite the fact that the idebenone therapy had not been discontinued. However, even a two month low-dose tocotrienol supplementation led to the decrease of oxidative stress indexes and to parameter values that approached those of healthy controls. Moreover, there are evidences that a longer tocotrienol treatment may be more effective in reducing oxidative stress.