In ataxia-teleangiectasia betamethasone response is inversely correlated to cerebellar atrophy and directly to antioxidative capacity

Background and purpose: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by alterations of the A-T mutated (ATM) gene. Although A-T is a noncurable disease, we, previously, documented a clear improvement of cerebellar functions during a short-term betamethasone trial. The aim of this study was to define the underlying biochemical mechanism. Methods: In six A-T patients receiving a short-term steroid therapy, intracellular glutathione (GSH) levels were evaluated with a colorimetric assay. The lipid peroxidation level and reactive oxygen species (ROS) production were evaluated using commercial assays. All the parameters were compared with the improvement of cerebellar functions expressed as delta (Δ) of the Scale for the Assessment and Rating of Ataxia (SARA). Results: We observed an inverse correlation between Δ SARA and the severity of cerebellar atrophy and between the latter and basal GSH values. Four of the five patients with the highest Δ SARA also had the highest GSH values. Moreover, even though basal ROS values were comparable in patients and controls, in the only patient studied at different time-points of therapy, a remarkable reduction in ROS levels was documented. Conclusion: We suggest that antioxidative mechanisms play a role in favouring the improvement of cerebellar functions observed in A-T patients receiving a short-term betamethasone trial.