A0001 in Friedreich ataxia: Biochemical characterization and effects in a clinical trial†‡§¶

This study tested the ability of A0001 (a-tocopheryl quinone; EPI-A0001), a potent antioxidant, to improve in vitro measures, glucose me- tabolism, and neurological function in Friedreich ataxia. We used an in vitro study of protection from cell toxic- ity followed by a double-blind, randomized, placebo- controlled trial of 2 doses of A0001 in 31 adults with Friedreich ataxia. The primary clinical trial outcome was the Disposition Index, a measure of diabetic tend- ency, from a frequently sampled intravenous glucose tolerance test, evaluated 4 weeks into therapy. Sec- ondary neurologic measures included the Friedreich Ataxia Rating Scale. A0001 potently inhibited cell death in Friedreich ataxia models in vitro. For the clinical trial, mean guanine-adenine-adenine repeat length was 699, and mean age was 31 years. Four weeks after treat- ment initiation, differences in changes in the Disposi- tion Index between subjects treated with A0001 and placebo were not statistically significant. In contrast, a dose-dependent improvement in the Friedreich Ataxia Rating Scale score was observed. Patients on placebo improved 2.0 rating scale points, whereas patients on low-dose A0001 improved by 4.9 points (P 5 .04) and patients on a high dose improved by 6.1 points (P < .01). Although A0001 did not alter the Disposition Index, it caused a dose-dependent improvement in neurologic function, as measured by the Friedreich Ataxia Rating Scale. Longer studies will assess the reproducibility and persistence of neurologic benefit. V C 2012 Movement Disorder Society