Core Viewpoint - The article discusses the significant breakthrough in spinal cord injury (SCI) treatment through the discovery of Thiorphan, a drug that promotes neuronal regeneration and functional recovery after SCI, offering new hope for patients suffering from paralysis and disability [2][3][6]. Group 1: Research Findings - A study published in Nature identified Thiorphan as a candidate drug that reprograms neurons to enhance recovery after spinal cord injury [3]. - Thiorphan, originally developed as a neutral endopeptidase inhibitor for treating diarrhea, has shown remarkable potential in promoting nerve regeneration and functional recovery in SCI models [11][19]. - In experiments with adult mice, Thiorphan increased total neurite growth by 80% and the longest neurite length by 30%, demonstrating a dose-dependent effect [12]. Group 2: Experimental Validation - In a rat model of severe cervical spinal cord injury, treatment with Thiorphan initiated two weeks post-injury resulted in a twofold increase in forelimb grasp success rate, improving accuracy from 30% to 60% when combined with neural stem cell transplantation [14]. - Anatomical evidence indicated that Thiorphan treatment led to a 60% increase in the regeneration of corticospinal axons, establishing synaptic connections across the injury site [15]. - Thiorphan was also effective in promoting growth in cortical neurons from both adult macaques and a 56-year-old human, with increases of 30.3% in total neurite growth and 23% in the longest neurite length [16]. Group 3: Mechanism of Action - The mechanism of Thiorphan involves upregulating brain-derived neurotrophic factor (BDNF) and phosphorylated AKT, allowing neurons to revert to a developmental state and regain growth capabilities [17]. - Given that Thiorphan has been safely used in humans, the clinical development risk is significantly reduced [19]. Group 4: Future Directions - The research team is exploring more convenient administration methods, including intrathecal injection or systemic delivery, and developing derivatives with better blood-brain barrier permeability [20]. - This study not only identifies a promising candidate for SCI treatment but also establishes a new paradigm for drug development from computer screening to human validation, which could be applied to other neurological and neurodegenerative diseases [20].