Although our results did not implicate a particular HDAC isoform for therapeutic targeting, the data presented here demonstrate that all class I and class II HDACs are present in human HD and in HD model mice throughout the disease course, and highlight their activities as attractive targets for chronic drug treatment. Developing brain-permeable class- and isoform-selective inhibitors with low predicted toxicity is an important therapeutic goal for medicinal chemistry optimization, which in its initial thrust can employ the inhibitors tested in this study. This evidence concerns the gene HDAC9 and Huntington disease.