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Scientists in Germany reportedly succeeded for the first time in getting mice to walk again after a complete cross-sectional injury using gene therapy. Paralysis resulting from a spinal cord injury has been irreparable so far. But now, the study by the Department for Cell Physiology at Ruhr-Universität Bochum (RUB) enabled the nerve cells to produce the curative protein themselves.
With a new therapeutic approach, the keys to this are the protein hyper-interleukin-6, which stimulates nerve cells to regenerate, and the way how it is supplied to the animals. The researchers published their report in the Journal Nature Communications in mid-January 2021.
Spinal cord injuries can be caused by a variety of circumstances, such as car accidents, truck accidents, or even by playing sports. Just like the brain, the spinal cord cannot regrow new cells. Therefore, victims of spinal cord injuries are often left to deal with lifelong disabilities, including paralysis from the neck down (quadriplegia) or paralysis from the waist down (paraplegia).
A recent estimate showed that the annual incidence of spinal cord injury is approximately 54 cases per one million people in the U.S., or about 17,730 new cases each year. According to Statista, the estimated lifetime cost of a patient who is 25 years old and suffering from paraplegia in the U.S. was around $2.5 million as of 2019.
Disabilities are caused by damage to nerve fibers, so-called axons, which carry information from the brain to the muscles and back from the skin and muscles. If these fibers are damaged due to an injury or illness, the communication is interrupted. And since severed axons in the spinal cord can’t grow back, the patients suffer from paralysis and numbness for life. To date, there are still no treatment options that could restore the lost functions in affected patients.
In their search for potential therapeutic approaches, the Bochum team induced nerve cells of the motor-sensory cortex to produce hyper-Interleukin-6 themselves. They used viruses suitable for gene therapy, which they injected into an easily accessible brain area. There, the viruses deliver the blueprint for the production of the protein to specific nerve cells, so-called motoneurons. Since these cells are also linked via axonal side branches to other nerve cells in other brain areas that are important for movement processes, like walking, the hyper-interleukin-6 was also transported directly to these otherwise difficult to access essential nerve cells and released there in a controlled manner.
Professor Dietmar Fischer, who headed the study, reportedly explained: “[The] 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. 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.”
The research team is now investigating to what extent this or similar approaches can be combined with other measures to optimize the administration of hyper-Interleukin-6 further and achieve additional functional improvements. They are also exploring whether hyper-interleukin-6 still has positive effects in mice, even if the injury occurred several weeks previously. Professor Fischer noted that this would be particularly relevant for application in people. “These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future,” he concluded.