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Large-scale data sets identify small RNAs with a role in epilepsy

A new paper from Jørgen Kjems' group at iNANO and MBG describes how expression of non-coding RNA changes during epileptic seizures in rodents. The authors found that inhibiting a specific set of microRNAs (miRNAs) by antisense technology reduced seizure frequency in a mouse model, suggesting that these RNA molecules could serve as possible targets for future epilepsy therapy.

Jørgen Kjems (left) og Morten T. Venø describes in an article in PNAS, how expression of non-coding RNA changes during epileptic seizures in rodents (Photo: Anne Færch Nielsen)

Epilepsy is a neurological disorder characterised by recurrent epileptic seizures and it displays a wide range in severity (from mild to highly debilitating) and in susceptibility to treatment. Temporal lobe epilepsy (TLE) is a type of epilepsy characterized by seizures that arise from the hippocampus. Many TLE patients do not respond to drug treatment, often necessitating surgical resection of the brain structures affected.

Jørgen Kjems and co-workers extracted brain tissue from three different rodent epilepsy models before and after the onset of epileptic seizures and used Next Generation Sequencing to map changes in expression of small non-coding RNAs. A set of miRNAs was found to respond to seizures in a similar manner in all three animal models, suggesting a general role in epilepsy rather than a species-specific effect.

The authors went on to show that inhibition of these epilepsy-regulated miRNAs upon injection of antisense RNA strands reduced the rate of spontaneous seizures in a mouse model. While the underlying molecular mechanism behind this effect remains unclear, bioinformatics and proteomics work suggested the TGF? signaling pathway to be involved.

The study is a result of more than four years of work in different labs in EpimiRNA and the authors hope that the large amount of sequencing data generated can serve as a resource for future studies on the molecular basis for epilepsy. The paper 'A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy' is published in the journal Proceedings of the National Academy of Sciences (PNAS).

The work, published in the journal PNAS, was spear-headed by former MBG/INANO-postdoc Morten Venø - now the CEO of AU spin-off company Omiics - and performed in close collaboration with the EU-funded consortium EpimiRNA. The consortium provided state-of-the-art animal models for epilepsy, which were analysed for disease-relevant RNA-expression by the Kjems lab. 

For further information, please contact

Professor Jørgen Kjems
Center for Cellular Signal Patterns (CellPAT)
Interdisciplinary Nanoscience Center (iNANO)
Institut for Molekylærbiologi og Genetik
Aarhus Universitet
+45 28992086 - jk@mbg.au.dk

Morten T Venø, PhD 
CEO, omiics ApS      
+45 28 72 71 07 - morten.veno@omiics.com