Anti-epileptogenic effect of NRP2945 in the pilocarpine model of temporal lobe epilepsy.

Innovative therapeutic strategies are highly needed to tackle the major medical needs of epilepsy, like prevention of epilepsy development in at-risk individuals, treatment of severe and drug-resistant forms, control of co-morbidities. The Neural Regeneration Peptide NRP2945 (a peptidomimetic analogue of the human CAPS-2 protein) has been recently found to exert many potentially anti-epileptic effects, for example increased neuronal survival and differentiation. In the present study, we tested the effects of NRP2945 on the development of epilepsy (epileptogenesis) and on chronic, spontaneous seizures, by using the pilocarpine model of temporal lobe epilepsy. We found that NRP2945 exerts a robust anti-epileptogenic effect, reducing the frequency of spontaneous seizures, exerting a significant neuroprotective effect and attenuating anxiety-like behaviors and cognitive impairment. These effects appear to depend on modulation of the epileptogenesis process and not on seizure suppression, because NRP2945 did not reduce frequency or duration of spontaneous seizures when administered to already epileptic animals. These findings may form the basis for a preventive therapy for individuals at-risk of developing epilepsy.