Rituximab beyond oncology: targeting B-cell-mediated immunomodulatory therapy in neurodegenerative and...

Neurological and neuropsychiatric disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), are associated with neuroinflammation, oxidative stress, protein aggregation, and blood-brain barrier disruption. This review aimed to evaluate the immunomodulatory and neuroprotective potential of rituximab in these disorders and summarize its mechanisms of action, therapeutic efficacy, and clinical limitations.

A comprehensive review of preclinical and clinical studies investigating rituximab in neurodegenerative and neuropsychiatric disorders was conducted. Relevant evidence regarding B cell-mediated pathology, rituximab's mechanisms of action, therapeutic outcomes, adverse effects, and emerging clinical applications was analyzed and synthesized.

Rituximab, a chimeric monoclonal antibody targeting CD20-positive B cells, exerts therapeutic effects through complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and apoptosis induction. In MS, rituximab reduces pro-inflammatory cytokines, immune cell activation, and demyelination, thereby slowing disease progression. Preclinical findings in AD and PD suggest that rituximab mitigates B cell-mediated neuroinflammation and oxidative stress, contributing to neuroprotection. Furthermore, rituximab has demonstrated clinical efficacy in AE, NMOSD, and MOGAD by depleting pathogenic B cells and reducing relapse frequency. However, treatment-associated complications such as hypogammaglobulinemia, infections, and infusion-related reactions remain significant concerns requiring careful monitoring and dose optimization.

Rituximab represents a promising immunomodulatory therapy for several neurological and neuropsychiatric disorders driven by B cell-mediated pathology. Its ability to modulate neuroinflammation and immune dysfunction highlights its therapeutic potential in neuroimmunology. Future studies should focus on improving central nervous system penetration, identifying predictive biomarkers of response, and exploring combination therapies to enhance efficacy and safety outcomes.