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The spinal cord is one of the most important parts of the body—it is essentially a bundle of nerves that runs down the back and carries signals back and forth between different parts of the body and brain. Spinal cord injuries (SCIs) disrupt these signals by damaging the spinal cord. The two kinds of spinal cord injuries—complete and incomplete—are categorized by the degree of damage done onto the spinal cord. Complete injury means the body is completely paralyzed below the injury, while an incomplete one entails some retainment of movement control and sensation below the injury.
Prone to severe paralysis, SCIs are medical emergencies. With immediate medical treatment, long-term effects can be reduced. However, a wholly effective treatment does not exist at the moment, particularly regarding immediate restoration of motor and sensory function after the injury. This is due to a lack of understanding of the complex biological processes behind a spinal cord injury.
To better understand this complex process, Skinnider and his research team integrated data from decades of smaller studies. They found that M3 group genes were most strongly linked to the severity of injury in both mice and rats. In fact, annexin A1, a gene in the M3 group, could perfectly differentiate between moderately and severely injured rats. Jordan Squair, a lead author of the study, concluded, “We have identified gene signatures that predict injury severity and, if reversed therapeutically, could potentially increase functional recovery.”
Another reason for the lack of fully effective treatment for SCIs is the absence of information regarding nerve regeneration in humans. Nerve regeneration is the ability of animals like frogs, dogs, whales, and snails to regrow nerves after an injury. Humans and primates, however, do not possess this ability. However, in an older study conducted at the Salk Institute of Biological Studies, it was found that the protein p45 promotes nerve regeneration by preventing the axon sheath from inhibiting regrowth.
The problem is that humans, primates, and other advanced vertebrates lack this p45 protein; instead, they have the protein p75, which binds to the myelin when there is nerve damage. A newer study at the Salk Institute found that growth-promoting p45 could disrupt p75 pairing, which latches onto inhibitors released from the damaged myelin. Axons were able to grow with fewer p75 pairs available to bind to inhibitors.
These findings implicate important therapeutic advancements. Introducing p45 protein to injured neurons or a small molecule that could jam the link between the p75 proteins could serve as a potential therapy to spinal cord damage. The next step will be to see if introducing p45 helps regenerate damaged human nerves.
References
Mayo Clinic Staff. (n.d.). Spinal cord injury. Retrieved October 13, 2018, from Mayo Clinic website: https://www.mayoclinic.org/diseases-conditions/spinal-cord-injury/diagnosis-treatment/drc-20377895
Squair, J. W., Tigchelaar, S., Moon, K.-M., Liu, J., Tetzlaff, W., Kwon, B. K., . . . Skinnider, M. A. (2018). Integrated systems analysis reveals conserved gene networks underlying response to spinal cord injury. eLIFE. https://doi.org/10.7554/eLife.39188
Vilar, M., Sung, T.-C., Chen, Z., García-Carpio, I., Fernandez, E. M., Xu, J., . . . Lee, K.-F. (2014). Heterodimerization of p45–p75 Modulates p75 Signaling: Structural Basis and Mechanism of Action. PLOS Biology. https://doi.org/10.1371/journal.pbio.1001918