Researchers from the University of British Columbia have discovered a gene signature tied to the severity of spinal cord injuries in animals and humans that will switch on or off in response to the injury.
While there are no widely available treatments able to restore motor and sensory functions immediately after spinal cord injuries, the researchers believe more insight on the genes could lead to the discovery of biomarkers that predict recovery and pinpoint new targets for treatment.
One of the hurdles preventing better spinal cord treatments is that scientists do not currently fully understand the complex cascade of biological processes that happen when a spinal cord injury occurs.
“Our understanding of the pathophysiological processes triggered by spinal cord injury is fragmentary,” senior author Michael Skinnider, a medical and PhD student at the University of British Columbia, said in a statement. “We set out to integrate the data from decades of small-scale studies using a systems biology approach.”
The team reviewed more than 500 studies to locate 695 unique human genes that are associated with the response to spinal cord injuries. From there, they were able to narrow down 151 of the genes that were linked in multiple studies.
To discover whether the genes truly reflect functional changes after a spinal cord injury, the researchers developed a network of genes from healthy human spinal cords. They were able to then integrate the data derived from the network with the data taken from the previous experimental studies they reviewed.
The found that the M3 and M7 groups of genes include a significant amount of genes that have been shown in experiments to be important in the response of a spinal cord injury.
The researchers further looked at five experimental studies of gene expression in mice and rats after spinal cord injuries to see whether any groups were significantly altered. The team found at least four gene groups, including the aforementioned M3 and M7, were switched on, and two other gene groups were switched off.
However, some of the groups were not as connected in the mice and rats as they were in humans. This suggests that these genes could be human-specific biomarkers for spinal cord injuries. Other groups were only important a specific time after an injury, which means that they are involved in the transition from acute to chronic injuries.
The researchers also narrowed down the M3 genes as the group most strongly linked to injury severity in the rodents, suggesting that they could be the ideal biomarker to predict the severity of the injury. In particular, annexin A1, which has been associated with spinal cord injuries in the past, is the one gene in the M3 group that was able to perfectly differentiate between moderately and severely injured rats when used as a biomarker.
“We have developed an integrated, systems-level approach to understand the mechanisms of spinal cord injury,” lead author Jordan Squair, a MD and PhD student at the University of British Columbia, said in a statement. “We have identified gene signatures that predict injury severity and, if reversed therapeutically, could potentially increase functional recovery.”
The study was published in eLife.
