Anticonvulsant effects of botulinum neurotoxin type E (BoNT/E)

Temporal Lobe Epilepsy (TLE) is one of the most common forms of human epilepsy and is burdened by a high rate of refractoriness to medical therapy. One therapeutic option currently under investigation in experimental models, is the delivery of anticonvulsant agents with long-lasting action directly into the seizure focus in the brain. Botulinum neurotoxin E (BoNT/E) is a bacterial protease that exert a prolonged blockade of synaptic activity by cleaving the synaptosomal-associated protein of 25 KDa (SNAP-25). Here we demonstrate by extracellular recordings and immunodetection of BoNT/E-cleaved SNAP-25 that BoNT/E effects persist for at least 14 days in the injected hippocampus. We also investigate the anticonvulsant properties of intrahippocampal injections of BoNT/E in a mouse model of TLE, in which limbic recurrent seizures follow kainic acid-induced status epilepticus. Preliminary data indicate that BoNT/E delivery is anticonvulsant on chronic paroxysmal discharges in this model of TLE.