New Treatment Regrows Complete Spinal Cord Injury In Mice

In 1990, legendary soul /funk artist Curtis Mayfield was struck in the back of his neck by a falling light fixture during a live performance. The falling light crushed 3 of his cervical vertebrae and completely severed his spinal cord, rendering him a quadriplegic for the rest of his life. Injuries like Mayfield’s are normally considered untreatable.

Unlike peripheral nervous tissue, central nervous tissue, such as the brain or spinal cord, will not spontaneously regenerate and form new connections. Axons in the central nervous system are relatively short and do not have the intrinsic growth capacity of neurons in the peripheral nervous system, so they cannot bridge the gap to restore connectivity and communication with the brain.

Mayfield died in 1999, long before any viable treatment options existed for those with spinal cord injuries. Now, in a new study published August 29 in Nature, biomedical researchers report that they have successfully stimulated neuron growth across the separation of a complete spinal cord injury. At this point, the regrowth treatment only works for one particular kind of cell in the spinal cord, but the success of initial treatments gives the researchers optimism that they can successfully develop regrowth treatments for other kinds of spinal cord cells. A process to effectively treat severe spinal cord injuries has long been desired, but medical professionals have been unable to figure out how to stimulate CNS tissue repair. The pendulum may begin to swing the other way though, as according to Mark Anderson, neurobiologist at UCLA and one of the lead authors on the study, “we now know what it takes.”

How To Fix A Complete Spinal Cord Injury

After a few trial and error procedures, the researchers realized the three important criteria for spinal cord repair, (1) the need for neurons with an intrinsic growth capacity, (2) a substrate to help the neurons bridge the spinal cord gap, and (3) particular chemoattractors to guide neurons growth in the appropriate locations and directions. None of these mechanisms will work alone, but in combination, they will yield successful neuron growth.

To fulfill the first criterion, the team utilized what are known as propriospinal neurons. Propriospinal neurons are web-like networks of cells that connect different parts of the spinal cord to each other. Propriospinal neurons are known for having a high intrinsic growth capacity and for forming spontaneous connections. Recent work has shown that propriospinal neurons can repair and preserve limited functioning in cases of partial spinal cord injury, so the researchers hypothesized that they could use propriospinal neurons to connect a complete spinal cord injury. However, just introducing chemicals to stimulate propriospinal neuron growth was not enough. The team also had to figure out how to get them to grow in the right place.

With regard to (2) the researchers used what is known as laminin, an extracellular protein found in the human body. Laminin plays a role in mammalian embryonic development where it functions as a kind of “scaffolding” around which tissue and organs form. Laminin has also found a use as a scaffolding for tissue engineering. Despite being readily present during embryonic development, mechanisms promoting laminin production are mostly absent in adult mammals. The researchers introduced certain growth factors to stimulate the production of laminal in the mice around their spinal cord injuries hoping that the growing propriospinal neurons would latch onto the laminin.

Lastly, the team needed a way to get the propriospinal neurons to grow in the appropriate direction across the spinal cord gap. They used a particular chemoattractor to coax the neurons to grow in the direction across the spinal cord. The chemoattractor binds to receptors in the propriospinal neurons and the neurons respond by growing in the direction of the chemical stimulus.

With a combination of these three mechanisms, the researchers were able to induce an “unprecedented amount” of propriospinal tissue growth across the spinal cord; over 100-fold more than control groups. Whats more, the new neurons penetrated well past the dead neural tissue at the ends of the spinal cord lesions to form robust synaptic connections with the spared neural tissue, returning a significant amount of electrical communication between the brain and spinal cord.

Going Forward: Therapeutic Use?

Despite the successful regrowth of CNS tissue in mice and rats, the researchers recommend against overexaggerating the potential for immediately therapeutic use in humans. Most likely, the procedure is only effective for the growth of propriospinal neurons, and new specific treatments will have to be created for other kinds of spinal neurons. “I very much suspect that we might need different combinations or combinations of different things for different populations of neurons,” senior researcher Michael Sofroniew told Scientific American.

Moreover, recovering from a spinal cord injury involves more than just the regrowth of spinal tissue. The mice and rats did not suddenly regain movement capabilities once their spinal cords were reconnected. Just like muscles, neurons have to be regularly exercised to become and remain strong. Newly grown neurons have to be trained to perform their function, which involves repetition and repeated activation of the neurons. Without rehabilitation, new neurons will not know what to do and will remain functionally ineffectual. The next step for the team involves combining the regrowth treatment with different kinds of post-treatment rehabilitation like electrophysiological stimulation or simple movement training.

As it stands though, the new study represents a significant advance in our understanding of spinal cord injuries and the mechanisms that go into fixing a spinal cord injury. Ideally, the three-criteria method will serve as a generally applicable schema for developing regrowth treatments for different kinds of neurons.