A new therapeutic approach enables recovery of function after spinal cord injury in mice

Using gene therapy, a research team has been successful for the first time in getting mice to walk again after a cross-sectional injury. The nerve cells secreted the medicinal protein themselves.

To date, paralysis resulting from spinal damage has been unstable. With a new therapeutic approach, scientists from the Department of Cell Psychology at Ruhr-Universität Bochum (RUB) led by Professor Dietmar Fischer have for the first time succeeded in getting mice to walk paralyzed. -rithist. The keys to this are the hyper-interleukin-6 protein, which stimulates zero cells to regenerate, and the way it is given to the animals. The researchers published their report in the Journal of Nature Communications as of January 15, 2021.

When the communication breaks down

Spinal cord injuries as a result of sports or traffic accidents often lead to permanent disabilities such as paraplegia. This is caused by damage to nerve fibers, called axons, which carry information from the brain to the muscles and back from the skin and muscles. If these fibers are damaged as a result of injury or illness, this communication is broken. Because broken axons in the spinal cord cannot grow back, the patients suffer from paralysis and anxiety for life. To date, there are still no treatment options that can reverse the lost functions in affected patients.

Design proteins promote regeneration

In their search for potential therapeutic modalities, the Bochum team has been working with the protein hyper-interleukin-6.

This is called a design cytokine, which means it does not happen like this in nature and must be realized using genetic engineering. “

Dietmar Fischer, Professor, RUB

His research group has already shown in a previous study that hIL-6 can stimulate nerve cell regeneration in the visual system.

In their current study, the Bochum team stimulated zero cells of the motor-sensory cortex to produce hyper-Interleukin-6 themselves. For this purpose, they used viruses suitable for gene therapy, which entered an easily accessible brain area. There, the viruses deliver the plan for the production of the protein to specific zero cells, called motoneurons. Because these cells are also connected through axonal side branches to other zero cells in other brain areas that are important for movement processes such as walking, the hyper-interleukin-6 was transported directly to these areas. it was difficult to get into essential zero cells and release them there in a controlled manner.

Engaged in one area, effective in several areas

“Thus, gene therapy treatment of only a few zero cells stimulated axonal regeneration of different nerve cells in the brain and several motor pathways in the spinal cord at the same time,” notes Dietmar Fischer. “Ultimately, this allowed the previously paralyzed animals who received this treatment to start walking after two or three weeks. This came as a big surprise to us at first, because it was never confirmed. that it was previously possible after full paraplegia. “

The research team is now investigating the extent to which this or similar approaches can be combined with other measures to maximize administration of hyper-Interleukin-6 and achieve further functional improvements. They are also investigating whether hyper-interleukin-6 has a positive effect in mice, even though the injury occurred several weeks earlier. “This aspect would be particularly relevant for advocacy in humans,” Fischer confirms. “We are now breaking new scientific ground. These other experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”

Source:

Magazine Reference:

Leibinger, M., et al. (2021) Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice. Nature Communication. doi.org/10.1038/s41467-020-20112-4.

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