Natalizumab analogon therapy is effective in a B cell-dependent multiple sclerosis model

Area of Science:

• Neuroimmunology
• Immunotherapy
• Multiple Sclerosis Pathogenesis

Background:

• Natalizumab, a CD49d-targeting monoclonal antibody, is approved for relapsing-remitting multiple sclerosis (MS).
• B cells and plasma cells are implicated in MS pathogenesis.
• Previous studies on natalizumab analogs primarily used T cell-mediated MS models.

Purpose of the Study:

• To investigate the efficacy of the natalizumab analog PS/2 IgG in a mouse model of MS involving both T and B cell cooperation (OSE mice).
• To assess the impact of PS/2 IgG on disease course, demyelination, and immune cell infiltration in this model.

Main Methods:

• OSE mice were treated with PS/2 IgG or its F(ab')2 fragments at disease onset or peak.
• Effects on clinical outcome, spinal cord pathology, and immune cell markers were evaluated.

Main Results:

• Early PS/2 IgG treatment significantly improved clinical outcomes, reduced spinal cord demyelination, and decreased immune cell infiltration.
• Treatment led to increased blood leukocytes and partial CD49d internalization on T and B cells.
• Therapeutic effects were observed with both PS/2 IgG and F(ab')2 fragments, indicating Fc-independent activity.
• Late-stage treatment with PS/2 IgG was ineffective.

Conclusions:

• Early intervention with natalizumab analogs like PS/2 IgG shows therapeutic potential in MS models with T and B cell involvement.
• The findings suggest that natalizumab may also be beneficial for MS driven by B cell immunopathogenesis.
• Fc-independent mechanisms contribute to the therapeutic effects of PS/2 IgG in this MS model.