Trial of d-α-tocopherol in Huntington's disease

Objective: Evidence suggests that the neuropathology of Huntington's disease, a neuropsychiatric disorder due to a mutation on chromosome 4, results from excessive activation of glutamate-gated ion channels, which kills neurons by oxidative stress. Therefore, the authors hypothesized that α-tocopherol, which reduces oxyradical damage to cell membranes, might slow the course of Huntington's disease. Method: A prospective, double-blind; placebo-controlled study of high-dose d-α-tocopherol treatment was carried out with a cohort of 73 patients with Huntington's disease who were randomly assigned to either d-α-tocopherol or placebo. Patients were monitored for changes in neurologic and neuropsychologic symptoms. Results: Treatment with d-α-tocopherol had no effect on neurologic and neuropsychiatric symptoms in the treatment group overall. However, post hoc analysis revealed a significant selective therapeutic effect on neurologic symptoms for patients early in the course of the disorder. Conclusions: Antioxidant therapy may slow the rate of motor decline early in the course of Huntington's disease.