Biomarker discovery and use in Spinal Cord Injury patients: Identifying new treatment targets and markers for predicting clinical outcome

Jessica Fisher-Stokes, Sharon Owen, Charlotte Hulme, Mateus Bernardo-Harrington, Joy Chowdhury, Aheed Osman, Srinivasa Budithi, Naveen Kumar, Paul Cool and Karina Wright

Funded by the Orthopaedic Institute and the Midland Centre for Spinal Injuries (MCSI), Oswestry

The spinal studies team has continued its work on identifying potential biomarkers in the bloods of patients following a spinal cord injury (SCI) in order to assist in the prediction of clinical outcomes. Recent work looking into the analysis of plasma samples in SCI patients is currently being reviewed for publication. This work identified several biomarkers in the samples that were biologically relevant and have the potential to predict clinical outcomes, many of which have implicated the liver as playing a role in the outcomes of patients post-injury.

Following this, the team is now looking into more targeted analysis of previously identified markers of injury from blood samples. Patient samples are currently being assessed with the use of enzyme linked immunosorbent assays (ELISAs) (see image 1 ) to determine the concentrations of 2 biomarkers of interest; S100 calcium binding protein B (S100ß), a protein secreted by cells of the central nervous system, and neurofilament light (NF-L), an important structural element of neurons.

Statistical techniques are then being used to determine their potential in predicting neurological outcome in SCI patients. So far, S100ß has shown to be statistically significant inpatients between the acute (2-week) and sub-acute (3-month) time point, as well as at the acute time point depending on if they are improvers or non-improvers (see image 2).

We are also beginning to investigate inflammatory markers for their potential as SCI biomarkers. Preliminary work investigated levels in patient serum samples of 9 different inflammatory identified two markers as being of interest, interleukin-1 receptor antagonist (IL-1RA) and interleukin 6 (IL[1]6), which will also be examined using ELISA techniques. It is hoped that these biomarkers will be able to be used alongside current clinical treatment and help aid rehabilitation decisions to allow patients to achieve the best clinical outcome possible.

The team is also beginning to collect blood samples from SCI patients admitted with pressure sores. These sores are a large problem for patients as they can extend recovery time due to the increased bed rest needed to heal the sores, with spinal injury centers subsequently being unable to free beds for new SCI cases. It is hoped that by investigating markers found in the blood of patients with pressure sores, alongside wound fluids in the future, will help us to understand the occurrence more clearly and often recurrence of the sores, and what factors aid in healing.

Alongside this work, the team is working in collaboration with the University of Glasgow and the NHS Greater Glasgow and Clyde to investigate routine blood scores from their patient population. We previously assessed ~500 patients’ blood samples from our hospital to determine which markers that were routinely assessed in the clinical setting would be able to accurately predict patient outcomes. The external dataset we have been given access to from Glasgow will allow us to run the same analysis using their patient data to validate our findings. This will also allow us to see if a different approach to patient management will affect which markers can predict outcomes; our site practices mainly conservative management of patients and surgeries are only recommended when absolutely necessary, whereas other spinal injury units regularly perform surgeries on SCI patients during the initial stage after injury.