CRITICAL REVIEW AND INVITED COMMENTARY
Inhibitory RNA in epilepsy: Research tools and therapeutic perspectives
Article first published online: 15 JUL 2010
Wiley Periodicals, Inc. © 2010 International League Against Epilepsy
Volume 51, Issue 9, pages 1659–1668, September 2010
How to Cite
Boison, D. (2010), Inhibitory RNA in epilepsy: Research tools and therapeutic perspectives. Epilepsia, 51: 1659–1668. doi: 10.1111/j.1528-1167.2010.02672.x
- Issue published online: 2 SEP 2010
- Article first published online: 15 JUL 2010
- Accepted May 19, 2010; Early View publication July 15, 2010.
- RNA interference;
- Gene therapy;
Since its discovery a decade ago, RNA interference (RNAi) has been developed not only into powerful experimental tools but also into promising novel therapeutics. In contrast to conventional antiepileptic drugs (AEDs) that target specific proteins such as ion channels or receptors, RNAi-based therapeutics exploit an endogenous regulatory mechanism of gene expression and thereby are poised to prevent or reverse pathogenetic mechanisms involved in seizure development. Therapeutic RNAi has been widely explored for dominant targets involved in neurodegenerative diseases; however, their use for epilepsy therapy has received less attention. This review discusses potential RNAi-based targets that are of interest for epilepsy therapy, including adenosine kinase (ADK), the key negative regulator of the brain’s endogenous anticonvulsant adenosine. Overexpression of ADK, and the resulting adenosine deficiency, are pathologic hallmarks of the sclerotic epileptic brain, and have been implicated in seizure generation. Therefore, RNAi-strategies aimed at reducing ADK (and increasing adenosine) are based on a direct neurochemical rationale that has recently been explored experimentally using ex vivo and in vivo gene therapy approaches. Technical issues and challenges remain before those promising tools can be developed into future therapeutics for epilepsy.