The dynamics of gene expression are regulated by
histone acetylases (HATs) and
histone deacetylases (HDACs) that control the acetylation state of
lysine side chains of the
histone proteins of
chromatin. The catalytic activity of these two
enzymes remodels
chromatin to control gene expression without altering gene sequence. Treatment of
cancer has been the primary target for the clinical development of
HDAC inhibitors, culminating in approval for the first
HDAC inhibitor for the treatment of
cutaneous T cell lymphoma. Beyond
cancer, HDAC inhibition has potential for the treatment of many other diseases. The
HDAC inhibitors phenylbutyric
acid,
valproic acid, and
suberoylanilide hydroxamic acid (SAHA) have been shown to correct errant gene expression, ameliorate the progression of disease, and restore absent synthetic or metabolic activities for a diverse group of non-
cancer disorders. These benefits have been found in patients with
sickle cell anemia, HIV, and
cystic fibrosis. In vitro and in vivo models of
spinal muscular atrophy,
muscular dystrophy, and neurodegenerative, and inflammatory disorders also show response to
HDAC inhibitors. This review examines the application of HDAC inhibition as a treatment for a wide-range of non-
cancer disorders, many of which are
rare diseases that urgently need
therapy. Inhibition of the HDACs has general potential as a pharmacological epigenetic approach for gene therapy.