Visualization of the entire spinal cord with regenerating projections protruding from the lower thoracic spinal cord to the center of locomotor execution. Credit: EPFL / .Neurorestore
Scientists at .NeuroRestore in Switzerland science They said they have developed a gene therapy that has been proven in mice to stimulate nerve regrowth across spinal cord injuries, guiding nerves to reconnect to their original targets and restore mobility.
When the spinal cord in mice or humans is partially injured, there is extensive and spontaneous recovery of motor function after initial paralysis. However, once the spinal cord is completely injured, natural repair of the spinal cord does not occur and it never recovers. Meaningful recovery after severe injury requires strategies that promote nerve fiber regeneration, but the conditions necessary for these strategies to successfully restore motor function remain unclear.
Previous discoveries and recent developments
“Five years ago, we demonstrated that nerve fibers can regenerate even in anatomically complete spinal cord injuries,” says Mark Anderson, senior author of the study. “But we also realized that this wasn’t enough to restore motor function because the new fibers couldn’t connect to the right place on the other side of the lesion.” Anderson explains how .NeuroRestore’s central nervous system regeneration Director and Scientist at the Wyss Center for Bio and Neuroengineering.
Visualization of the entire spinal cord with regenerating projections protruding from the lower thoracic spinal cord to the locomotor execution center. Credit: EPFL / .Neurorestore
Working collaboratively with colleagues at the University of California, Los Angeles (University of California Los Angeles) and Harvard Medical School researchers used state-of-the-art equipment at EPFL’s Campus Biotechnology Facility in Geneva to perform a detailed analysis of which types of neurons are naturally occurring after partial spinal cord injury. We have identified whether or not it is involved in spinal cord repair. “Our observations using single cell nuclei” RNA Sequencing not only revealed the specific axons that needed to regenerate, but also that these axons needed to reconnect to their natural targets to restore motor function. ” said Jordan Square, lead author of the study. The team’s findings will be published in the September 22, 2023 issue. science.
Towards a combination of approaches
Their findings have influenced the design of multifaceted gene therapies. The researchers activated a growth program in identified mouse neurons to regenerate nerve fibers, upregulating specific proteins to support neuron growth through the center of the lesion, and regenerating nerve fibers. Guidance molecules were administered to attract the natural target beneath the lesion. “We were inspired by nature when we designed a treatment strategy that mimics the spinal cord repair mechanisms that occur naturally after partial injury,” Square says.
Visualization of the entire spinal cord with regenerating projections protruding from the lower thoracic spinal cord to the locomotor execution center. Credit: EPFL / .Neurorestore
Mice with anatomically complete spinal cord injury recovered locomotor ability and exhibited a gait pattern similar to that quantified in mice that spontaneously resumed locomotion after partial injury. This observation reveals a previously unknown condition for regenerative therapy to successfully restore motor function after neurotrauma. “We hope that our gene therapy will work synergistically with other treatments that involve electrical stimulation of the spinal cord,” said senior author of the study and director of .NeuroRestore along with Jocelyne Bloch. says Grégoire Courtine. “We believe a complete solution to treating spinal cord injuries requires both approaches: gene therapy to regrow the involved nerve fibers, and gene therapy to regrow these fibers and the spinal cord underlying the injury. Both are spinal cord stimulation to maximize the ability to produce movement.”
Many hurdles still have to be overcome before this gene therapy can be applied to humans, but scientists are taking the first steps toward developing the technology needed to accomplish this feat in the coming years. I took a step.
Reference: “Recovery of locomotion after paralysis by regenerating characterized neurons into natural target areas” Jordan W. Squair, Marco Milano, Alexandra de Coucy, Matthieu Gautier, Michael A. Skinnider, Nicholas D. James , Newton Cho, Anna Lasne, Claudia Kathe, Thomas H. Hutson, Stephen Szeto, Letitia Bo, Katia Galan, Viviana Aureli, Achilleas Lascaratos, Quentin Barrow, Timothy J. Deming, Ritchie E. Korman, Bernard L. Schneider, Jegan He, Jocelyn Block, Michael V. Sofronew, Grégoire Courtteen and Mark A. Anderson, September 21, 2023. science.
DOI: 10.1126/science.adi6412
