What If a Blood Test Could Accurately Predict Potential Recovery from SCI?
The diagnosis of a spinal cord injury (SCI) and the subsequent determination of the patient’s potential for recovery rely on extensive clinical examinations and advanced imaging – a time-consuming, costly process that is especially challenging for patients with SCI-related complications.
Researchers at the Johns Hopkins University School of Medicine may have found a better way: They’ve developed a novel blood test that has the potential to rapidly predict severity and likelihood of sensory and motor recovery within 6 months in a cost-effective manner.
Not Your Typical Test
Clinicians have long sought a rapid, minimally invasive diagnostic method that confirms injury, severity, and recovery potential. The novel blood test, described in a report published by The Journal of Clinical Investigation, may fill this critical gap in care.
“If you have a spinal cord injury, your main question is simple: Am I going to walk again?” said lead study author and neurosurgery chief resident, Tej D. Azad, MD, MS.
“With the new blood test, we are trying to bring a precision medicine framework to spinal cord injury with something that tells you about injury severity and can hopefully predict neurological recovery.”
Classically, blood tests have not been considered to offer insights into the spine due to the blood-brain barrier. However, the Johns Hopkins researchers hypothesized that SCI causes measurable disruptions in the blood-brain barrier that are potentially detectable in a blood test.
Building on Cancer Research
To detect such biomarkers of SCI, the researchers built on recent advances in cancer biomarker development, where liquid biopsies of blood detect cell-free DNA (cfDNA) and certain protein levels guide targeted treatments for individual patients while also offering ways to monitor treatment response and disease progression.
“Using blood-based biomarkers for cancer diagnosis and progression has changed the practice of oncology,” said co-senior study author Nicholas Theodore, MD, director of the Johns Hopkins Neurosurgical Spine Center.
“Utilizing similar technology, this test is truly an example of personalized medicine in traumatic injury.”
The Spinal Cord Injury Index is Born
Researchers defined the fingerprint of spinal cord DNA using blood samples from 50 patients with acute SCI and 25 patients without injury, of which 68% (51 patients) were male and 32% (24 patients) were female.
The researchers also observed that cfDNA levels in blood samples correlated with the standard American Spinal Injury Association (ASIA) scale used to assess SCI severity based on motor and sensory function. Higher cfDNA concentrations were found in the ASIA A group — representing no sensation or function of motor skills — compared with less severe injuries with groups B (P = 0.04), C (P = 0.009), and D (P < 0.001), which suggests that greater spinal cord damage releases more cfDNA into the bloodstream.
To further refine the blood test’s accuracy, researchers identified 4 key blood plasma proteins — FABP3, REST, IL-6 and NF-H — that were elevated in patients with SCI.
The investigators call the resulting combination blood test the Spinal Cord Injury Index (SCII). When compared with ASIA groups, the results of SCII aligned completely with severity of injury and what would be seen on MRI scans and physical evaluations.
“These findings highlight the importance of a multi-analyte approach,” said senior study author and the Jennison and Novak Families Professor of Neurosurgery, Chetan Bettegowda, MD, PhD.
“Combining both DNA and protein-based biomarkers improves the test performance and biological relevance.”
Future Directions
Patients whose blood was used in the study were followed for 6 month assess whether their ASIA grade improved. The SCII effectively predicted with 77% accuracy which patients would show neurologic improvement. This suggests that the new blood test may accurately forecast long-term recovery for most patients, a central focus and concern for patients with SCI and their caregivers.
Researchers say using the SCII to monitor these biomarkers over time could further assist in measuring the effectiveness of treatment options and inform personalized care, as liquid biopsies inform care for cancer patients.
“We are interested in bringing a precision medicine framework to spinal cord injury,” said Dr. Azad. “By building this type of blood test, we can begin to sub-stratify these traditional groups, use therapies that may be more beneficial, and for patients who have most severe injury, we can expedite getting them into clinical trials.”
This multi-analyte blood test is a promising step toward next generation diagnostics for SCI and personalized medicine in traumatic injury. Dr. Bettegowda said further studies are required, as the team is now hoping to test the blood markers in multi-center clinical trials and study ways to improve its performance.
Source
Azad TD, Ran KR, Materi JD, et al. A multi-analyte blood test for acute spinal cord injury. J Clin Invest. 2025 Mar 3;135(5):e185463. doi: 10.1172/JCI185463.