Epigenetic approaches for bipolar disorder drug discovery

Bipolar disorder (BD) is a common psychiatric disorder which can be devastating to affected patients, if not adequately treated. Although effective drugs are presently available for treating BD, many patients do not respond adequately. There are also problems with the current management of patients with this disorder: drug-resistant BD, rapid-cycling BD and cognitive decline in BD patients despite drug therapy. In this context, new and more effective drugs will be valuable in the clinical management of BD patients.

This article discusses the potential of the use of epigenetic drugs in the management of BD. Although several classes of epigenetic drugs are under investigation, at present, most attention is focused on two classes of epigenetic drugs: DNA methyltransferase inhibitors and histone deacetylase inhibitors (HDACis). Several preclinical drug trials of HDACis for the treatment of BD have been conducted.

HDACis have shown promising results in preclinical studies of BD. However, the currently available HDACis suffer from acting non-specifically on HDAC isozymes. More isozyme-specific HDACis are likely to have greater efficacy and less toxicity than the current HDACis. It is suggested that efforts should be made to develop such HDACis. Once such HDACis with adequate ability to cross the blood-brain barrier become available, investigators could consider proceeding to clinical trials of HDACis for the treatment of BD.