Anti-mouse properdin TSR 5/6 monoclonal antibodies block complement alternative pathway-dependent pathogenesis

Area of Science:

• Immunology and Molecular Medicine
• Complement System Biology
• Therapeutic Target Identification

Background:

• The complement alternative pathway (AP) is implicated in numerous diseases, including age-related macular degeneration, atypical hemolytic uremic syndrome, and preeclampsia.
• Therapeutic strategies aiming to inhibit AP activity are of significant interest due to its role in disease pathogenesis.
• Properdin, the sole positive regulator of the AP, represents a critical and promising target for therapeutic intervention.

Purpose of the Study:

• To develop and characterize antibodies capable of blocking properdin function.
• To assess the therapeutic potential of targeting properdin for AP-mediated diseases.
• To evaluate the feasibility of properdin-directed therapies using preclinical models.

Main Methods:

• Expression of a mouse properdin protein fragment in a bacterial system.
• Generation of rabbit polyclonal and hamster monoclonal antibodies against mouse properdin.
• Utilizing AP-dependent mouse disease models to test the efficacy of the generated antibodies.

Main Results:

• Successfully raised antibodies that effectively block properdin-dependent pathogenesis.
• Demonstrated the utility of these antibodies in evaluating properdin-directed therapy in relevant disease models.
• Provided a foundation for further development of properdin-targeting therapeutics.

Conclusions:

• Antibodies targeting properdin can effectively inhibit AP-driven disease mechanisms.
• Preclinical models are valuable tools for assessing the therapeutic potential of properdin inhibitors.
• Properdin-directed therapies hold promise for treating a range of complement-mediated diseases.