title: Preventing epileptogenesis: A realistic goal?
abstract: The definition of the pathologic process of epileptogenesis has considerably changed over the past few years due to a better knowledge of the dynamics of the associated molecular modifications and to clinical and experimental evidence of progression of the epileptic condition beyond the occurrence of the first seizures. Interference with this chronic process may lead to the development of novel preventive therapies which are still lacking. Notably, epileptogenesis is often associated with comorbid behaviors which are now considered primary outcome measures for novel therapeutics. Anti-epileptogenic interventions may improve not only seizure onset and their frequency and severity but also comorbidities and cell loss, and when applied after the onset of the disease may provide disease-modifying effects by favorably modifying the disease course. In the preclinical arena, several novel targets for anti-epileptogenic and disease-modifying interventions are being characterized and validated in rodent models of epileptogenesis. To move proof-of-concept anti-epileptogenesis studies to validation in preclinical trials and eventually to clinical translation is a challenging task which would be greatly facilitated by the development of non invasive biomarkers of epileptogenesis. Biomarker discovery together with testing potential novel drugs would provide a major advance in the treatment of human epilepsy beyond the pure symptomatic control of seizures.
authors.affiliation: Department of Neroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; Department of Translational Medicine, Section of Pediatrics, Federico II University, Napoli, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Terrone
authors.affiliation: Department of Neroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pauletti
authors.affiliation: Department of Neroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Pascente
authors.affiliation: Department of Neroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. Electronic address: annamaria.vezzani@marionegri.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058256:Brain Waves / Q000187:drug effects*; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D015415:Biomarkers; D018836:Inflammation Mediators
keywords: Biomarkers; Disease-modifications; Experimental models of epileptogenesis