Glycine transporter 1 is a target for the treatment of epilepsy

Objective: One third of people with epilepsy respond poorly to existing anti-epileptic drugs (AEDs); besides, these drugs can be associated with side-effects. Hence, there is an urgent need to discover newer targets that AEDs can work on to decrease seizures. The authors of a recent paper studied a neurotransmitter called glycine and its role in epilepsy. Neuronal function depends on a fine balance between excitation and inhibition, and glycine plays a key role in maintaining this balance. Since seizures are can result from an imbalance between excitation and inhibition, it is reasonable to think that the role of glycine in epilepsy is valuable to investigate. The authors looked at the hippocampus because the hippocampus is greatly affected in temporal lobe epilepsy (TLE). Seizures were generated in experimental rats and mice and glycine in the hippocampus was observed.

Results: The effects of glycine in the hippocampus are mediated by the glycine transporter 1 (GlyT1). An increase in GlyT1 was observed in two experimental models of TLE and also in tissue from people with TLE. Since epilepsy was found to be associated with an increase in GlyT1, the question that followed was what would happen if GlyT1 action was decreased. In response to a drug that inhibits GlyT1, experimental animals were found to be protected from seizures.

Interpretation: This study showed that targeting glycine and GlyT1 could be investigated further for epilepsy. Of course, more research needs to be done, but the findings of this study provide a promising lead.

Summary for specialists