Drug Repurposing for Spinal Cord Injury: Progress Towards Therapeutic Intervention for Primary Factors and Secondary Complications

Spinal cord injury (SCI) encompasses a plethora of complex mechanisms like the involvement of major cell death pathways, neurodegeneration of spinal cord neurons, overexpression of glutaminergic transmission and inflammation cascade, along with different co-morbidities like neuropathic pain, urinary and sexual dysfunction, respiratory and cardiac failures, making it one of the leading causes of morbidity and mortality globally. Corticosteroids such as methylprednisolone and dexamethasone, and non-steroidal anti-inflammatory drugs such as naproxen, aspirin and ibuprofen are the first-line treatment options for SCI, inhibiting primary and secondary progression by preventing inflammation and action of reactive oxygen species. However, they are constrained by a short effective drug administration window and their pharmacological action being limited to symptomatic relief of the secondary effects related to spinal cord injury only. Although post-injury rehabilitation treatments may enable functional recovery, they take a long time to show results. Drug repurposing might be an innovative method for expanding therapy alternatives, utilising drugs that are already approved by various esteemed federal agencies throughout the world. Reutilising a drug molecule to treat SCI can eliminate the need for expensive and lengthy drug discovery processes and pave the way for new therapeutic approaches in SCI. This review summarises marketed drugs that could be repurposed based on their safety and efficacy data. We also discuss their mechanisms of action and provide a list of repurposed drugs under clinical trials for SCI therapy.

Automated summary

Spinal cord injury (SCI) is a leading cause of morbidity and mortality worldwide, involving complex mechanisms such as cell death pathways, neurodegeneration, glutaminergic transmission, and inflammation. Current treatment options, including corticosteroids and non-steroidal anti-inflammatory drugs, have limitations in their effectiveness and are focused on symptomatic relief. Drug repurposing offers a promising approach to expand therapy alternatives for SCI, utilizing approved drugs with known safety and efficacy data. This review summarizes marketed drugs that could be repurposed and discusses ongoing clinical trials for SCI therapy.