Evolving role of biomarkers in spinal cord injury: From research to clinical translation

Spinal cord injury (SCI) triggers a complex cascade of cellular and molecular events at the lesion site, driving progressive degeneration of the spinal cord. This increases the level of disability over time and also significantly diminishes the prospects of recovery. SCI also causes systemic changes that affect overall physiology and function. In this context, biomarkers detectable in body fluids-such as blood, urine, and cerebrospinal fluid-that reflect lesion-site events and correlate with recovery outcomes are critically important. Biomarker analysis can be leveraged for: a) research and drug discovery; b) confirming target engagement of therapies or drug delivery systems; c) optimizing dosage or dosing frequency to maximize outcomes; d) serving as early prognostic indicators; and e) enabling patient stratification and adaptive clinical trial design. Our comprehensive analyses of preclinical and clinical studies show that multiple biomarkers are common to both rodent models of SCI and humans with SCI. Notably, these biomarkers appear earlier and remain elevated for a shorter duration in rodents than in humans. Importantly, several of these biomarkers can predict injury severity and functional recovery. Artificial intelligence-driven analysis and interpretation of biomarker profiles can further transform early diagnosis and prediction of therapeutic outcomes. This review summarizes the current status, key challenges, and future prospects of biomarker-based approaches in SCI research and clinical trial design to accelerate therapeutic development.