ANTI-EPILEPTIC EFFECTS OF BOTULINUM TOXINS IN RODENT MODELS OF TEMPORAL LOBE EPILEPSY

Temporal lobe epilepsy (TLE) is a very common form of human epilepsy that in many cases is genetically determined. TLE is often the result of an early insult (e.g. febrile status epilepticus, head trauma) that induces rearrangements in the brain which lead, after a latent period of years, to chronic epilepsy. This latent phase is known as "epileptogenesis". Currently, there are no means to interfere with epileptogenesis. This means that despite pharmacological treatment, many patients continue to have seizures until adult age, and develop a form of the disease which is resistant to any known therapy. The development of new pharmacological tools able to block epileptogenesis is therefore of interest for the therapy of TLE. It is has been hypothesized that rearrangements of brain circuitry during epileptogenesis depend on the activity of nerve cells. Thus, new drugs specifically targeted to block nerve cell activity might be useful to treat the disease. In our study, we will test the efficacy of the bacterial enzyme Botulinum Toxin E (BoNT/E), which is known to block nerve cell activity, as a new selective drug against TLE. In particular, we will test whether intracerebral injections of BoNT/E are able to block epileptogenesis after the induction of status epilepticus in animal models of TLE. If positive, our results will indicate a way along which new strategies eventually applicable to TLE patients might be developed.