Numerous studies have pointed to histone deacetylase inhibitors as potential 
therapeutics for various neurodegenerative diseases, and clinical trials with 
several histone deacetylase inhibitors have been performed or are under way. 
However, histone deacetylase inhibitors tested to date either are highly 
cytotoxic or have very low specificities for different histone deacetylase 
enzymes. The authors' laboratories have identified a novel class of histone 
deacetylase inhibitors (2-aminobenzamides) that reverses 
heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich 
ataxia. The authors have identified the histone deacetylase enzyme isotype 
target of these compounds and present evidence that compounds that target this 
enzyme selectively increase FXN expression from pathogenic alleles. Studies with 
model compounds show that these histone deacetylase inhibitors increase FXN 
messenger RNA levels in the brain in mouse models for Friedreich ataxia and 
relieve neurological symptoms observed in mouse models and support the notion 
that this class of molecules may serve as therapeutics for the human disease.