Gene Therapy Allows Paralyzed Mice To Walk Again

The protein hyper-interleukin-6 stimulates the regeneration of damaged nerve fibers. Image: whitehoune/Shutterstock.com

For the first time, researchers have managed to restore movement in mice that had suffered a “complete spinal cord crush”, thanks to the development of a signaling protein called hyper-interleukin-6 (hIL-6). Describing their methods in the journal Nature Communications, the study authors explain how they used gene therapy in order to stimulate the animals’ neurons to start producing the protein, causing the damaged nerve cells to regrow in just a few weeks.

At present, there are no effective treatments for the restoration of severed nerve fibers in the spinal cord. As such, people who suffer injuries resulting in significant damage to these fibers – also known as axons – often experience lifelong paralysis.

However, a team of researchers recently demonstrated that hIL-6 can in fact cause damaged axons to regenerate in the visual cortex. A type of signalling molecule known as a cytokine, hIL-6 does not occur naturally and can only be produced via genetic engineering.

To determine the cytokine’s effectiveness at repairing damaged spinal axons, the team injected the brains of injured mice with a virus that contained the necessary genetic code for the production of hIL-6. This virus was delivered directly into the rodents’ cortical motoneurons, which are easily accessible and communicate with other parts of the central nervous system that are much harder to reach, yet which are vital for movement processes like walking.

Most importantly, these cortical motoneurons are linked via axons to the raphe nuclei, which sit within the brainstem and are the primary producers of the neurotransmitter serotonin. This is particularly significant, since serotonin is known to play a crucial role in locomotor recovery following spinal cord injuries, yet the position of the raphe nuclei makes them impossible for researchers to access directly.

Following injection, the genetically altered motoneurons began producing hIL-6, which was then transported to the raphe nuclei, resulting in the regeneration of severed axons in multiple regions of the brain.

“Thus, gene therapy treatment of only a few nerve cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” explained study author Dietmar Fischer in a statement.

“Ultimately, this enabled the previously paralyzed animals that received this treatment to start walking after two to three weeks. This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia.”

This locomotor recovery was prevented when the researchers introduced a toxin that specifically targets serotonergic fibers, confirming the importance of the neurons within the raphe nuclei for the restoration of walking ability.

Based on these findings, it may one day be possible to use similar gene therapies in order to heal spinal injuries in paralyzed humans.

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