Adenosine kinase, glutamine synthetase and EAAT2 as gene therapy targets for temporal lobe epilepsy

Young D, Fong DM, Lawlor PA, Wu A, Mouravlev A, McRae M, Glass M, Dragunow M, During MJ.

Contributed by Sloka Iyengar

Gene Therapy September 2014 doi:10.1038/gt.2014.82

Anti-epileptic drugs (AEDs) work only via a few known targets; the authors of a recent study investigated whether astrocytes could prove to be a potential avenue for novel AED discovery. Adeno-associated viral (AAV) vector was used to overexpress glutamine synthetase (GS) and excitatory amino-acid transporter 2 (EAAT2) to increase synaptic glutamate clearance. Additionally, microRNA technique was used to decrease expression of the enzyme adenosine kinase (ADK), and increase synaptic levels of adenosine – a naturally occurring anticonvulsant. It was found that altering GS or EAAT2 did not affect seizures or neurodegeneration, but increasing adenosine levels did lead to a decrease in kainate-induced seizures and afforded neuroprotection.

Summary for non-specialists