AGING MODULATES DISEASE PROGRESSION, MYELOID CELL RESPONSES, AND TREATMENT RESPONSE IN THE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS MODEL

Multiple sclerosis (MS) is a common autoimmune demyelinating disorder affecting the myelin sheath surrounding neurons in the brain and spinal cord. Usually identified in young adults, aged between 20 and 40, MS patients can experience various physical, cognitive, and psychiatric symptoms.
Experimental Autoimmune Encephalomyelitis (EAE) is a well-established and widely used mouse model to investigate human autoimmune disorders such as MS.
This project aims at defining age-dependent differences in immune cell number and morphology in EAE mice and assess the therapeutic efficacy of remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, thereby improving translational relevance and effectiveness of therapeutic strategies.
The MOG35-55 peptide EAE model was induced in young (6-8 weeks) and old (10 months) C57BL/6 mice, which were treated with a daily oral dose of 3 mg/kg bodyweight remibrutinib; aged-matched EAE mice received a vehicle solution.
Our results indicate that the age of disease onset significantly affects EAE clinical progression; after peak of disease, younger animals recover, while older animals continue to exhibit high EAE scores.
Immunohistochemical analysis and three-dimensional quantification of Iba1-positive myeloid cells showed a significant increase of Iba1-positive cells numbers and larger altered morphology in EAE animals compared to controls.
Furthermore, preliminary results indicate aged and young EAE groups respond different to treatment with remibrutinib.
Our findings indicate significant differences between young and aged EAE models in clinical outcomes, disease course, and immunological profiles. This study emphasizes aging as a critical comorbidity and suggest that accounting for age-related effects may improve translational relevance and therapeutic efficacy.