Therapeutic inhibition of the alternative complement pathway attenuates chronic EAE

Area of Science:

• Immunology
• Neuroscience
• Pathology

Background:

• The alternative complement pathway is a major driver of pathology in demyelinating diseases.
• Current treatment options for the chronic phase of demyelinating diseases are limited.

Purpose of the Study:

• To evaluate the therapeutic potential of inhibiting the alternative complement pathway using an anti-factor B antibody in a mouse model of multiple sclerosis.
• To assess the impact of factor B inhibition on both acute and chronic phases of the disease.

Main Methods:

• Utilized experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis.
• Administered a monoclonal antibody (mAb 1379) targeting mouse factor B.
• Assessed disease onset, acute phase, and chronic phase, including cellular infiltration, inflammation, and demyelination.

Main Results:

• Anti-factor B antibody treatment did not affect the onset or acute phase of EAE.
• Significantly attenuated the chronic phase of EAE, reducing cellular infiltration, inflammation, and demyelination.
• Long-lasting attenuation of chronic disease was observed even after antibody treatment cessation.
• Similar therapeutic effects were seen in transferred EAE models using MOG-specific T cells.

Conclusions:

• Inhibition of factor B demonstrates significant therapeutic potential for managing the chronic phase of demyelinating diseases.
• Targeting the alternative complement pathway offers a promising strategy for conditions with limited treatment options.