Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy

Adenosine is an inhibitor of neuronal activity in the brain. The local rele ase of adenosine from grafted cells was evaluated as an ex vivo gene therap y approach to suppress synchronous discharges and epileptic seizures. Fibro blasts were engineered to release adenosine by inactivating the adenosine-m etabolizing enzymes adenosine kinase and adenosine deaminase. After encapsu lation into semipermeable polymers, the cells were grafted into the brain v entricles of electrically kindled rats, a model of partial epilepsy. Crafte d rats provided a nearly complete protection from behavioral seizures and a near-complete suppression of afterdischarges in electroencephalogram recor dings, whereas the full tonic-clonic convulsions in control rats remained u naltered. Thus, the local release of adenosine resulting in adenosine conce ntrations < 25 nM at the site of action is sufficient to suppress seizure a ctivity and, therefore, provides a potential therapeutic principle for the treatment of drug-resistant partial epilepsies.