29/05/2024 Thesis Defense by Vincent Escarrat

Wednesday 29th May 2024, at 14:30, Bâtiment principal Salle de thèse N°2

Vincent Escarrat (Equipe MRS)

EVALUATION OF THE THERAPEUTIC INTEREST OF PHOTOBIOMODULATION ON A MOUSE MODEL OF MULTIPLE SCLEROSIS

Jury:
Directeur de these     M. Franck DEBARBIEUX     INT, AMU
CoDirecteur de these     M. Rémi BOS     INT
Rapporteur     Mme Anne DESMAZIèRES     ICM
Rapporteur     M. Denis VIVIEN     BB@C, UNICAEN
Examinateur     Mme Sophie UGOLINI     CIML
Examinateur     Mme Cécile MORO     CEA-Leti
Président     M. Valéry MATARAZZO     INMED
Examinateur     M. Jacques TOUCHON     Université de Montpellier/Faculté de médecine

Abstract: Translation: Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease that affects more than 2.8 million people worldwide. The disease leads to irreversible disability caused by the progressive onset of functional and cognitive impairments. Significant advances in identifying the cellular players in MS have led to the development of around fifteen disease-modifying treatments (DMTs). These DMTs, mainly applicable to Relapsing-Remitting forms, help alleviate MS symptoms but carry the risk of inducing numerous, sometimes severe, adverse effects. There is thus a real need to better understand the underlying mechanisms of MS pathophysiology to develop new, more effective therapeutic modalities with a more favourable safety profile. Photobiomodulation Therapy (PBMT), which employs near-infrared light wavelengths to stimulate biological tissues and reduce inflammation, has recently garnered attention for treating neurological disorders. During this 3 years work, we aimed to evaluate its non-invasive therapeutic potential in the context of MS and understand its effects on the cellular interactions involved in neuroinflammation and neurodegeneration. We conducted a longitudinal and multimodal study on the murine model of experimental autoimmune encephalomyelitis (EAE), combining intravital imaging on a unique line of multi-fluorescent transgenic mice, in vivo assessment of functional deficits, five-colour immunofluorescence, and ex vivo electrophysiological recordings. We demonstrated that non-invasive dorsoventral PBMT substantially reduced inflammation and axonal loss, prevented neuronal hyperexcitability, and improved functional deficits. Interestingly, through observed spinal effects at both dorsal and ventral levels, our results suggest a systemic action of PBMT. Furthermore, its action on both early and late inflammatory components suggests therapeutic potential for its application at all stages of the disease. This preclinical study thus provides solid evidence of the effectiveness of non-invasive PBMT without side effects in the context of MS. With the major advantage of modulating inflammation without harmful complete immunosuppression, it could easily be translated into clinical practice. PBMT thus represents an innovative therapeutic option for MS, as well as for other inflammatory diseases. Key words: SEP, non-invasive PBMT, EAE, neuroinflammation, neurodegeneration, functional deficits, electrophysiology, fluorescent imaging, intravital microscopy.