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A randomized, double-blind, crossover, placebo-controlled clinical trial of oral isoniazid was undertaken in eight men with known Huntington's disease. Six completed the trial. Overall chorea scores indicated some amelioration, but clinical improvement was noticed in only two patients and was mild. Side effects included anorexia and elevation of liver enzyme levels. Cerebrospinal fluid (CSF) and plasma gamma-aminobutyric acid (GABA) concentrations were measured simultaneously. Mean CSF GABA increased threefold following treatment with isoniazid (414 +/- 52 SEM pmol/ml) compared to placebo (120 +/- 11 pmol/ml). No significant changes occurred in plasma GABA levels between the placebo and drug treatment phases. Reversal of central GABA deficiency appears not to correct extrapyramidal symptoms in Huntington's disease.

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