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Prospects for the development of epigenetic drugs for CNS conditions

Abstract

Advances in our understanding of the epigenetic mechanisms that control gene expression in the central nervous system (CNS) and their role in neuropsychiatric disorders are paving the way for a potential new therapeutic approach that is focused on reversing the epigenetic underpinnings of neuropsychiatric conditions. In this article, the complexity of epigenetic processes and the current level of proof for their involvement in CNS disorders are discussed. The preclinical evidence for efficacy of pharmacological approaches that target epigenetics in the CNS and the particular challenges of this approach are also examined. Finally, strategies to address these challenges through the development of improved evidence-based epigenetic therapeutics and through combining pharmacological and behavioural approaches are presented.

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Figure 1: Rationale for epigenetic drugs, reversibility of epigenetic reactions, and epigenetic states and sites of pharmacological modulators.

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Acknowledgements

Work in the laboratory of M.S. is supported by the Canadian Institute of Health Research (MOP-42411) and the Sackler Program in Psychobiology and Epigenetics at McGill University, Montreal, Canada.

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Szyf, M. Prospects for the development of epigenetic drugs for CNS conditions. Nat Rev Drug Discov 14, 461–474 (2015). https://doi.org/10.1038/nrd4580

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