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Identifying New Drug Disease Connections for Spinal Cord Injury

  • Author(s): Riley, Theresa Marie
  • Advisor(s): Tuszynski, Mark H
  • et al.
No data is associated with this publication.
Abstract

Spinal cord injury (SCI) is a widespread and drastic condition that causes permanent paralysis below the level of the lesion, as well as a myriad of associated problems. In the past, efforts to promote regeneration have remained largely unsuccessful. Recent work from the Tuszynski lab reported that grafts of spinal cord neural progenitor cells (NPCs) or neural stem cells (NSCs) grafted into sites of SCI support extensive corticospinal tract (CST) regeneration into the lesion site. This finding was significant because the CST is the most important motor system in humans and efforts to maximize regeneration of this system are key to developing translational human therapies. The regenerating transcriptome of the CST was identified, showing neurons underdoing active regeneration display a sustained upregulation of gene expression over time. We mapped our regenerating transcriptome signature onto the Broad Connectivity Map (CMAP). Our CST regeneration signature was queried against 1.3 million signatures, where a positive match showed a similar transcriptome profile to our CST signature. In silico analysis identified Thiorphan as a candidate drug that most closely resembles the transcriptome of our regenerating CST signature. In vitro, Thiorphan caused an increase in neurite outgrowth compared to control. When tested in a cervical contusion lesion, thiorphan treatment alone showed an increase in functional recovery after SCI compared to lesion-only controls. When used in combination with NPC graft, no additive benefit was seen. In conclusion, there may be a new drug-disease connection between Thiorphan and spinal cord injury.

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This item is under embargo until January 7, 2023.