Senolytics repurposing in childhood refractory epilepsies

Introduction

Epilepsy is a frequent neurological disorder characterized by recurrent seizures resulting from hyperexcitability and hypersynchrony of neuronal networks. Cortical malformations, including Focal Cortical Dysplasia (FCD), are rare sporadic diseases that cause early-life drug-resistant seizures for which surgery is the only therapeutic option to control seizures. Surgical inaccessibility and failures are significant clinical drawbacks. This emphasizes a critical and urgent need for new precision-based therapies for this debilitating childhood disorder.

Recent Discoveries

In recent years, my team contributed to revealing that FCD are caused by brain somatic mutations in genes belonging to the mTOR pathway, a signaling cascade regulating key physiological cell functions such as growth, proliferation, and metabolism. During the course of my ERC-funded project, we discovered specific biomarkers in both human and mouse preclinical FCD brain tissues.

Proposed Strategy

In EpiSen, we propose an innovative pharmacological strategy based on the selective elimination of mutated cells by repurposing available molecules that are currently used in clinical trials in other diseases for FCD-related epilepsy.

Hypothesis

We hypothesize that abnormal cells, once acutely cleared, will offer a prolonged benefit on seizures.

Stakeholders

Direct users include:

• Applied research groups
• Pharma companies
• The medical community for clinical trials
• Patient associations