Thiorphan reprograms neurons to promote functional recovery after spinal cord injury.

ABSTRACT: We previously identified an embryonic shift in the corticospinal motor neuronal transcriptome after spinal cord injury associated with successful axonal regeneration¹. Exploiting this transcriptional regenerative 'signature', here we used in silico screens to identify small molecules that generate similar shifts in the transcriptome, and identified thiorphan-a neutral endopeptidase inhibitor-as a lead candidate. In a new adult motor cortex neuronal in vitro screen², thiorphan increased neurite outgrowth 1.8-fold (P < 0.001). We then infused thiorphan into the central nervous system beginning 2 weeks after severe C5 spinal cord contusions and, when combined with a neural stem cell graft, thiorphan elicited significant improvements in forelimb function (P < 0.005) and c

SUBMITTER: van Niekerk EA 

PROVIDER: S-EPMC12695623 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature