Researchers have used a “designer cytokine” to regenerate injured nerves in the spinal cords of mice with paraplegia. The treatment restored the ability to walk after only 2–3 weeks.
Following an injury, the neurons of adults do not naturally regenerate their axons — the long projections that carry nerve signals from the brain via the spinal cord to the muscles.
This helps explain why spinal cord injuries often cause severe and permanent disability, including paralysis of the lower half of the body, known as paraplegia.
For decades, scientists have investigated ways to regenerate neurons, but there is currently no cure for paraplegia.
In 2013, neuroscientists in Germany published a study showing that an immune signaling protein — or cytokine — called interleukin-6 (IL-6) could promote the regeneration of optic nerve axons in lab cultures.
IL-6 can have various effects on the immune system, such as encouraging platelet release to enable blood clot formation. But the 2013 research suggested that it could also facilitate the healing of nerve cells.
One hurdle, however, concerned how to deliver the cytokine to inaccessible parts of the central nervous system that are critical for restoring movement.
Another difficulty is that natural IL-6 has a relatively weak stimulatory effect on nerve regeneration.
Now, members of the same team and colleagues, all based at Ruhr-University Bochum, in Germany, have developed a technique that delivers a “designer” version of IL-6 deep into the central nervous system.
They have tested their technique in mice with paraplegia as a result of severe spinal cord injury, with promising results.
The study has been published in Nature Communications.
Powerful stimulatory effect
In previous research, the team demonstrated that the artificial interleukin, called hyper-IL-6, has a more powerful stimulatory effect on molecular regeneration than natural IL-6.
In the new experiment, they used a genetically engineered virus to introduce the genetic instructions for making hyper-IL-6 into motor neurons in an outer region of the brain called the sensorimotor cortex.
The advantage of this “gene therapy” approach is that it allows cells infected with the virus to make their own hyper-IL-6.
The protein is then distributed via branching axons to more distant, inaccessible parts of the central nervous system that are essential for movement, where it triggers regeneration.
“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,” explains senior author Dr. Dietmar Fischer.
Paralyzed animals that received a single injection of the virus began to walk again after 2–3 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,” says Dr. Fischer.
Dr. Fischer’s lab is now investigating ways to combine the new technique with other promising approaches, such as using tissue grafts to bridge the spinal injury site.
In addition, they are exploring whether hyper-IL-6 can regenerate neurons even if the spinal injury occurred several weeks earlier.
Dr. Fischer explains:
“This aspect would be particularly relevant for application in humans. We are now breaking new scientific ground. These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”
It should be noted that all the research to date has involved animal models of spinal cord injury. Many years of further work will be necessary to develop and test a safe, effective treatment for humans.
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