Antiepileptic mechanisms of AppCH2ppA in the model of Tuberous Sclerosis Complex

Abstract

Tuberous Sclerosis Complex (TSC) is a rare genetic disease characterized by the presence of epileptic crises that appear early in life and often resist to pharmacological approaches. These crises are considered as a main risk factor for the development of other neurological disorders associated to TSC. Thus, it is crucial to develop more efficient novel compounds to treat as early as possible the crises and prevent development of a complex neurological syndrome. In this work we describe the powerful antiepileptic properties of AppCH2ppA in a mouse model for TSC. We showed that AppCH2ppA stimulates an endogenous antiepileptic pathway naturally recruited in epileptic contexts and based on the enhancement of adenosine signalization through A1 receptors. Furthermore, we confirmed antiepileptic properties of AppCH2ppA on human patients’ tissue and general in vitro epileptic model. Finally, the administration of AppCH2ppA is not associated with significant side effects on general health of the treated mice highlighting that this compound represents a good candidate to further explore and could be a promising tool to treat resistant epileptic crises in human.

Jury

Christophe PORCHER – Président – Inmed, Marseille
Bertrand LAMBOLEZ – Rapporteur – IBPS, Paris
Sylvain RHEIMS – Rapporteur – Hôpital Pierre Wertheimer, Bron
Natalia LOZOVAYA – Examinateur – Neurochlore, Marseille

Thesis defense – Alexandre PONS BENNACEUR
Inmed meeting room, Friday September 24th, 2 p.m.