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NEUROLOGY 1982;32:354
© 1982 American Academy of Neurology

A double-blind clinical trial of isoniazid in Huntington disease

Thomas L. Perry, M.D., James M. Wright, M.D., F.R.C.P.(C), Ph.D., Shirley Hansen, B.A., Shirley M. Baker Thomas, M.D., F.R.C.P.(C), Barbara M. Allan, M.D., F.R.C.P.(C), Patricia A. Baird, M.D., F.R.C.P.(C) and Patricia A. Diewold, M.A.

Departments of Pharmacology, (Drs. Perry and Wright and Ms. Hansen), Medicine, (Dr. Allan), Medical Genetics, (Dr. Baird), and Psychiatry, (Ms. Diewold), University of British Columbia, and Dr. Thomas, Vancouver, Canada.

Isoniazid (INH) was given to nine patients with Huntington disease (HD) in a double-blind, placebo-controlled crossover trial. In an earlier open trial, three of six patients had improved, and one of them remained improved after 7 years on INH. Only one patient benefited in the present trial. All patients excreted small amounts of hydrazine in their urine while taking INH, and it is this INH metabolite that elevates GABA content in brain. GABA concentrations were markedly increased in CSF during INH therapy. Lack of clinical improvement in most HD patients despite elevation of brain GABA content suggests that in the minority who are benefited, INH may be acting by some mechanism other than increase of GABAergic neuronal function.

Address correspondence and reprint requests to Dr. Perry, Department of Pharmacology, University of British Columbia, Vancouver, British Columbia V6T 1W5, Canada.

This study was supported by grants from the Medical Research Council of Canada, the Hereditary Disease Foundation, and the British Columbia Health Care Research Foundation.

Accepted for publication September 21, 1981.






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