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Post-traumatic stress disorder (PTSD)

Histone deacetylase 2 (HDAC2)

Mouse studies suggest HDAC2 inhibitors could help treat PTSD associated with long-term traumatic memories. In mice receiving a fear-extinction treatment protocol 1 day after fear conditioning, compared with mouse models receiving the protocol after 30 days, conditioned fear responses decreased and Hdac2-chromatin dissociation in hippocampal neurons increased. In mice receiving the protocol 30 days after conditioning, a class I HDAC inhibitor decreased conditioned fear responses and increased synaptic and structural plasticity of hippocampal neurons compared with vehicle. Future studies could include developing and testing HDAC2-specific inhibitors in the mouse models.
Acetylon Pharmaceuticals Inc. has ACY-738, a selective inhibitor of HDAC1 and HDAC2, in preclinical testing to treat neurological indications.
Acetylon also has a selective HDAC1 and HDAC2 inhibitor in preclinical testing to treat sickle cell disease and thalassemia (see PTSD: rewriting fearful memories, page 9).

SciBX 7(4); doi:10.1038/scibx.2014.122
Published online Jan. 30, 2014

Patent and licensing status unavailable

Gräff, J. et al. Cell; published online
Jan. 16, 2014;
Contact: Li-Huei Tsai, Massachusetts Institute of Technology,
Cambridge, Mass.