NextCure Publishes Non-Clinical Data Demonstrating Anti-Siglec-15 Treatment Prevented Bone Loss Due to Immobilization from Acute Spinal Cord Injury
Following spinal cord injury, patients typically suffer rapid and extensive bone loss. While anti-resorptive therapies have shown some efficacy in inhibiting bone loss, these agents also inhibit bone formation. In preclinical testing, NC605 has been shown to prevent bone loss by inhibiting osteoclast maturation and bone resorption by binding S15, which is expressed on the cell surface of immature osteoclasts and upregulated in differentiated osteoclasts. Unlike anti-resorptive therapies, NC605 enhances osteoblast recruitment, resulting in overall enhanced bone quality.
“Bone loss due to severe immobilization is rapid, progressive and severe. Skeletal fragility in patients with immobilization injuries, including many veterans under long term care in
In the animal model of spinal cord injury, bone mineral density (BMD) was assessed and compared to control animals. Key findings from the study include:
- Treatment with anti-S15 antibody completely prevented loss of BMD in the femur and tibia.
- High-resolution imaging analysis revealed almost complete prevention of trabecular bone volume loss.
- Blood and bone structure analyses revealed that the anti-S15 antibody was able to greatly inhibit bone resorption while maintaining bone formation and quality.
- Ex vivo analysis showed increased numbers of osteoblasts as well as increased levels of mRNA encoding osteocalcin and bone sialoprotein (BSP), markers of bone formation and integrity, demonstrating a unique ability of the antibody to reduce osteoclast formation and bone resorption while promoting osteoblast recruitment to maintain bone integrity.
The data were generated in collaboration with Dr.
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Source: NextCure