Multiple sclerosis: molecular pathogenesis and therapeutic intervention

Abstract

Multiple sclerosis; Molecular pathogenesis; Therapeutic intervention

Esclerosi múltiple; Patogènesi molecular; Intervenció terapèutica

Esclerosis múltiple: Patogénesis molecular; Intervención terapéutica

Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system characterized by demyelination, axonal loss, and neuroinflammation, culminating in progressive neurological disability. Despite significant advances in understanding its immunopathogenesis, current immunotherapies remain limited in their ability to halt disease progression, making multiple sclerosis incurable and highlighting the critical need for novel therapeutic strategies. Antigen-specific immunotherapy represents a groundbreaking approach that aims to restore immune tolerance to myelin-derived antigens while preserving the protective functions of the immune system. Unlike broad immunosuppressive strategies, antigen-specific immunotherapy offers the potential for highly targeted modulation of pathogenic immune responses, reducing off-target effects and enhancing safety profiles. Over the last two decades, preclinical studies and clinical trials have explored diverse antigen-specific immunotherapy modalities, ranging from peptide-based vaccines to nanoparticle platforms, each aimed at achieving durable tolerance in multiple sclerosis. This review provides a comprehensive overview of multiple sclerosis, covering its etiology, clinical features, pathogenesis, pathology, and current therapeutic approaches. Thus, it delves into the current state of antigen-specific immunotherapy research, critically examining its successes and limitations while addressing the translational challenges that must be overcome to realize its therapeutic potential. By integrating insights from immunology, biotechnology, and translational medicine, we propose directions for advancing antigen-specific approaches in the quest for transformative multiple sclerosis therapies.

This project has received funding from the MCIN/AEI/10.13039/501100011033 and the European Union-NextGenerationEU/PRTR through the CPP2021-008475 project. This work was also supported by the “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR; Generalitat de Catalunya) through Consolidated Research Groups 2021SGR00782.