Development of an innovative radiotherapy using Synchrotron X-rays to treat drug-resistant epilepsy

On Friday October 17th 2025, Loan SAMALENS will defend his thesis "Development of an innovative radiotherapy using Synchrotron X-rays to treat drug-resistant epilepsy".

This thesis has been directed by Antoine Depaulis of the "Functional Neuroimaging and Brain Perfusion" team of the GIN and Raphaël Serduc of the STROBE team.

Jury composition

- Professeure Catherine Belzung, Université de Tours, rapporteure 
- Professeure Louise Tyvaert, Praticienne hospitalière, Université de Nancy, rapporteure 
- Professeur Camille Very, Praticien hospitalier, CHU Grenoble, examinateur 
- Raphaël Serduc, Chargé de recherche, INSERM, co-directeur de thèse 
- Antoine Depaulis, Directeur de recherche émérite, INSERM, directeur de thèse
 

Abstract

Despite the variety of existing treatments, around 30% of patients remain drug-resistant, particularly in mesio-temporal lobe epilepsy (MTLE), which is often associated with hippocampal sclerosis and cognitive and emotional comorbidities. Although resective surgery is effective, it remains invasive and carries risks. Microbeam Radiation Therapy (MRT), made possible by the unique properties of synchrotron X-rays, allows extremely high doses to be delivered via microbeams while sparing healthy tissue. However, its potential had never been evaluated in epilepsy. In a first study, we confirmed that the KA-MTLE mouse model reproduces several clinical features observed in patients, including an increased risk of SUDEP (Sudden Unexpected Death in Epilepsy), reduced well-being, and hyperactivity resembling ADHD (Attention Deficit Hyperactivity Disorder). The second study showed that multi-trajectory MRT irradiation (2 and 5 ports) significantly reduced seizures without toxicity, unlike single-port irradiation. Finally, the third study demonstrated a robust and long-lasting (≥ 8 months) antiepileptic effect of 5-port MRT compared to conventional radiotherapy, with good tissue tolerance. Depending on the dose, MRT modulated certain comorbidities: weight loss and increased hyperactivity at high dose (500 Gy), and improved cognitive performance at a lower dose (125 Gy). These findings provide the first preclinical evidence supporting the efficacy of MRT for refractory MTLE and open the way for innovative clinical applications.

Keywords: Radiotherapy, Microbeam Radiation Therapy, Mesio-Temporal Lobe Epilepsy, Hippocampus, Comorbidities