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

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