Failure of aminooxyacetic acid therapy in Huntington disease.

Seven patients with Huntington disease were treated with aminooxyacetic acid (AOAA), an inhibitor of gamma-aminobutyric acid aminotransferase (GABA-T), in an effort to alleviate symptoms by increasing brain GABA content. AOAA was given orally in a placebo-controlled crossover trial in which patients, relatives, and three of the evaluating physicians remained blind. Toxic symptoms occurred in all seven patients when AOAA dosage was increased beyond 2 mg per kilogram per day, and included drowsiness, ataxia, seizures, and psychotic behavior. In five patients who took AOAA for 4 months, no clinical improvement was observed. Biochemical monitoring showed that less inhibition of hepatic GABA-T enzyme activity was achieved than in patients treated with large doses of isoniazid. Results of this trial neither support nor exclude the possible therapeutic usefulness of increasing brain GABA content in Huntington disease.