Novel frontiers in epilepsy treatments: preventing epileptogenesis by targeting inflammation

Abstract

Currently available epilepsy drugs only affect the symptoms (seizures), and there is a need for innovative treatments that target the underlying disease. Increasing evidence points to inflammation as a potentially important mechanism in epileptogenesis. In the last decade, a new generation of etiologically realistic syndrome-specific experimental models have been developed, which are expected to capture the epileptogenic mechanisms operating in corresponding patient populations, and to exhibit similar treatment responsiveness. Recently, an intervention known to have broad-ranging anti-inflammatory effects (selective brain cooling) has been found to prevent the development of spontaneously occurring seizures in an etiologically realistic rat model of post-traumatic epilepsy. Several drugs used clinically for other indications also have the potential for inhibiting inflammation, and should be investigated for antiepileptogenic activity in these models. If results of such studies are positive, these compounds could rapidly enter Phase III trials in patients at high risk of developing epilepsy.

Keywords::

• clinical trials
• disease modification
• drug treatment
• epilepsy
• epileptogenesis
• experimental models
• hypothermia
• inflammation
• traumatic brain injury

Financial & competing interests disclosures

R D’Ambrosio is supported by the University of Washington and NIH grant NS076570. R D’Ambrosio has previously received consultancy fees and research support from Johnson & Johnson Pharmaceuticals, LLC. C Fattore is supported by the National Institute of Neurology IRCCS C Mondino Foundation (Pavia, Italy). E Perucca is an employee of the University of Pavia and has received grants from the EU, the Italian Medicines Agency, the Italian Ministry of Health, the Italian Ministry for Education, University and Research and the National Institute of Neurology IRCCS C Mondino Foundation. E Perucca has also received speaker’s or consultancy fees and/or research grants from Eisai, GSK, Medichem, Supernus, UCB Pharma, Upsher-Smith, Vertex and Viropharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.