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Updated: Nov 2, 2025
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Published on: October 14, 2025
Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury
Michael A Skinnider1, Jason Rogalski1, Seth Tigchelaar2
1Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
Insights
Researchers identified protein biomarkers in cerebrospinal fluid and serum to predict recovery from acute spinal cord injury (SCI). This discovery aids in evaluating new SCI treatments and guides future preclinical research.
Area of Science:
- Biochemistry
- Neuroscience
- Translational Medicine
Background:
- Clinical trials for acute spinal cord injury (SCI) treatments often fail due to reliance on lengthy neurological assessments.
- Current animal models for SCI research may not accurately reflect human injury, hindering therapeutic development.
- There is a critical need for objective, efficient outcome measures in SCI clinical trials.
Purpose of the Study:
- To develop novel protein biomarkers for assessing SCI severity and predicting neurological recovery.
- To establish reliable biochemical outcome measures for both human and animal SCI studies.
- To bridge the gap between preclinical research and clinical application for SCI therapies.
Main Methods:
- Targeted proteomic analysis of cerebrospinal fluid and serum from 111 acute SCI patients.
- Parallel proteomic analysis in a porcine model of SCI.
- Development and validation of a prognostic model for neurological improvement using identified biomarkers.
Main Results:
- Identified protein biomarkers indicative of SCI severity and recovery.
- Developed a prognostic model for 6-month neurological improvement with high accuracy (AUC 0.91).
- Established glial fibrillary acidic protein (GFAP) in cerebrospinal fluid as a cross-species biochemical outcome measure.
Conclusions:
- Protein biomarkers can significantly improve the efficiency and objectivity of SCI clinical trials.
- GFAP serves as a validated biochemical marker for SCI outcomes in both humans and pigs.
- This research facilitates the evaluation of novel SCI therapies and directs future preclinical investigations.
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