Wnt surrogate scFv-Dkk1c improves motor recovery and modulates glial reactivity in rat spinal cord injury.

Effective treatment for spinal cord injury (SCI) remains a significant challenge, with current therapies often failing to fully restore neurological function. Activation of canonical Wnt/β-catenin signaling holds therapeutic promise for SCI due to its roles in neuroprotection and regeneration. However, challenges like Wnt ligand production, high receptor cross-reactivity, and non-specific glycogen synthase kinase-3β (GSK-3β) inhibitors hinder Wnt-based drug development. Chimeric Wnt surrogates, designed to overcome these limitations, represent a crucial advancement, yet their specific benefits in SCI had not been previously explored.

Researchers evaluated the therapeutic effects of the canonical Wnt surrogate scFv-Dkk1c in a clinically relevant rat model of spinal cord injury (SCI). The study involved overexpression of scFv-Dkk1c during SCI progression. Key injury-related aspects were assessed, including motor functional recovery, myelin preservation, neuronal cell density, and the reactivity of microglia/macrophages and astroglia. They also examined markers related to astroglial and microglia/macrophage polarization, tissue vascularization, and descending serotonergic innervation. The primary endpoint was motor functional recovery, with various cellular and molecular markers as secondary endpoints.