Researchers at the University of Birmingham have identified 14 small non-coding RNAs in saliva that can diagnose a concussion with 96% accuracy, based on sample analysis from 1,028 professional rugby players.
Researchers at the University of Birmingham have identified 14 small non-coding RNAs (sncRNAs) in saliva that can diagnose a concussion with 96% accuracy, based on sample analysis from 1,028 professional rugby players.
Birmingham spinout Marker Diagnostics, which helped fund the study, is commercializing an over-the-counter concussion diagnostic for elite male athletes based on the panel, and the findings could lead to additional point-of-injury diagnostics for a broader population.
In the study–published in the British Journal of Sports Medicine–researchers first collected saliva samples from 106 players with concussions confirmed via clinical assessment, and 50 players with head injuries where concussions were ruled out. The Birmingham team then used next-generation sequencing to identify sncRNAs present at baseline, just after injury, post-game, and two days later.
The analysis identified 32 sncRNAs differentially expressed in concussed players, with 14 overexpressed over time following injury and another five underexpressed.
The researchers next tested the diagnostic value of the 14-sncRNA panel in a smaller group of players with head injuries, finding it was 91% accurate overall in distinguishing players with concussions from those without, and 96% accurate at the post-game sampling.
The mechanism through which sncRNAs correlating to brain injury appear in saliva remains unclear, but the researchers suggested that the detected sncRNAs originated from exosomes linked to cellular signaling. The exosomes could have been excreted by cranial nerves in the mouth and throat.
An accurate and rapid saliva diagnostic would improve safety and treatment for athletes at all levels. According to first author Valentina Di Pietro, a molecular neuroscientist at the University of Birmingham and consultant with Marker Diagnostics, “Concussion can be difficult to diagnose, particularly in settings such as grass roots sports where evaluation by a specialist clinician is not possible. Consequently, some concussions may go undiagnosed.”
A non-invasive diagnostic could help improve diagnosis consistency and accuracy, she added.
Concussions are considered mild traumatic brain injury and are typically confirmed with neuroimaging. But at the site of injury–when determinations are made whether further competition is appropriate, or whether medical attention is needed–assessments are made based on more subjective clinician assessment and patient self-reporting.
Marker Diagnostics, a subsidiary of Switzerland-based Marker AG, is commercializing the salivary sncRNA panel as MDx.100 for mild traumatic brain injury. The company is also performing additional trials in female athletes, young athletes and community sports players, with the goal of using the test to diagnose concussions outside of elite male athletes. Marker Diagnostics also plans to apply for U.S. Food and Drug Administration approval.
