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Computational Screen Identifies Thiorphan for Spinal Cord Injury With Strong Preclinical Gains

The Nature study repurposes a racecadotril metabolite by matching a regenerative gene signature to existing drugs.

Overview

  • UCSD researchers used an in silico platform that matched an embryonic-like transcriptional signature in corticospinal motor neurons to thousands of compounds and pinpointed thiorphan as a lead candidate.
  • Thiorphan promoted robust neurite outgrowth in adult human cortical neurons and in rhesus cortical cultures, validating effects in difficult-to-culture adult brain cells.
  • In rats with severe spinal cord injury, treatment produced about 50% greater recovery of hand function versus controls, with an additional ~50% improvement when combined with neural stem cell grafts and more regeneration into the lesion.
  • Direct infusion into the motor cortex was reported as safe and effective in the experiment, supporting a targeted delivery approach for central nervous system repair.
  • The team is optimizing brain delivery, testing blood–brain barrier permeability, and synthesizing derivatives while preparing for in-human testing, noting that prior safety data from racecadotril use may help de-risk advancement.