Complete visualization of regenerated nerve pathways originating from the lower thoracic region of the spinal cord that extend to centers responsible for ambulation. Credit: EPFL / .Neurorestore
Researchers at .NeuroRestore in Switzerland have published findings in the journal Science, presenting a gene therapy that has shown promise in mice for encouraging nerve re-growth across spinal cord injuries. This therapy aids nerves in reestablishing connections with their original targets, thereby reviving mobility.
In instances where the spinal cords of mice and humans sustain partial damage, the initial paralysis is often succeeded by a considerable, natural recuperation of motor function. However, in the case of full spinal cord injuries, such natural recovery processes do not take place, leaving no scope for functional improvement. Effective recovery after catastrophic injuries demands approaches that facilitate the re-growth of neural fibers, but the specific conditions under which these techniques can successfully reinstate motor functionality have hitherto been ambiguous.
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Antecedent Research and Current Advances
“Half a decade ago, we proved that neural fibers could be regenerated even after complete spinal cord injuries,” states Mark Anderson, a principal author of the research. “However, we understood that this was insufficient for the restoration of motor functions because the newly formed fibers failed to connect correctly beyond the injury site.” Anderson serves as the Director of Central Nervous System Regeneration at .NeuroRestore and is a researcher at the Wyss Center for Bio and Neuroengineering.
Cooperating closely with colleagues at the University of California, Los Angeles (UCLA) and Harvard Medical School, the researchers employed cutting-edge technology at EPFL’s Campus Biotech facilities in Geneva for thorough examinations. They identified the specific type of neuron responsible for natural spinal cord repair following partial injuries. “Through single-cell nuclear RNA sequencing, we not only identified the essential axons for re-growth, but also discovered that these axons need to be reconnected to their original targets to reinstate motor function,” notes Jordan Squair, the lead author of the study. These conclusions are published in the September 22, 2023, edition of Science.
Towards a Multi-faceted Therapeutic Strategy
Informed by this newfound understanding, the researchers developed a comprehensive gene therapy. They activated growth plans in the relevant neurons in mice, augmented particular proteins to sustain the growth of these neurons through the injury core, and applied molecular guidance to steer the regenerating nerve fibers towards their original targets. “Our therapeutic strategy was inspired by natural repair mechanisms that spontaneously occur after partial spinal injuries,” comments Squair.
Mice with fully damaged spinal cords regained their walking abilities, displaying locomotion patterns similar to those observed in mice that naturally resumed walking after partial injuries. This finding unveiled a hitherto unidentified prerequisite for regenerative treatments to effectively restore motor function post-neurotrauma. “We anticipate that our gene therapy will work in synergy with other treatments that involve electrical stimulation of the spinal cord,” says Grégoire Courtine, another principal author of the study who also co-leads .NeuroRestore along with Jocelyne Bloch. “We posit that a comprehensive solution for treating spinal cord injuries will necessitate both gene therapy for nerve re-growth and spinal stimulation to optimize the functional output of the regenerated fibers and the spinal cord below the injury.”
Although several challenges remain to be addressed before this gene therapy can be implemented in humans, the researchers have initiated the preliminary phases to develop the requisite technology for achieving this remarkable medical breakthrough in the foreseeable future.
Reference: “Restoration of Ambulation Following Paralysis by Guiding Characterized Neurons to their Native Target Areas” by 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 Steven Ceto, Laetitia Baud, Katia Galan, Viviana Aureli, Achilleas Laskaratos, Quentin Barraud Timothy J. Deming, Richie E. Kohman, Bernard L. Schneider, Zhigang He, Jocelyne Bloch, Michael V. Sofroniew, Gregoire Courtine, and Mark A. Anderson, 21 September 2023, Science.
DOI: 10.1126/science.adi6412
Frequently Asked Questions (FAQs) about Spinal cord regeneration
What is the primary focus of the research conducted by .NeuroRestore?
The research primarily focuses on developing a gene therapy that stimulates nerve re-growth across spinal cord injuries in mice, aiming to restore their mobility.
Who collaborated on this research project?
The .NeuroRestore team collaborated with colleagues from the University of California, Los Angeles (UCLA) and Harvard Medical School.
What methodologies were used for the research?
State-of-the-art equipment at EPFL’s Campus Biotech facilities in Geneva was used for in-depth analyses. The researchers employed single-cell nuclear RNA sequencing to identify specific neurons and axons involved in natural spinal cord repair.
What are the implications of this study for future treatment of spinal cord injuries?
The study represents a breakthrough in understanding how to promote nerve fiber regeneration and connection to their natural targets. Although the research is still in its early stages, it offers a promising pathway for the development of effective treatments for humans in the future.
What challenges remain for implementing this therapy in humans?
While the therapy has shown promise in mice, several obstacles must be overcome before it can be applied to humans. These include ensuring the safety and efficacy of the gene therapy and other synergistic treatments like electrical spinal cord stimulation.
Who are the principal authors and contributors to the study?
The principal authors of the study are Mark Anderson, who serves as the Director of Central Nervous System Regeneration at .NeuroRestore, and Jordan Squair, the lead author. Grégoire Courtine, who co-leads .NeuroRestore, is another key contributor.
What is the unique aspect of this gene therapy?
The gene therapy employs a multi-faceted approach. It activates growth programs in identified neurons, upregulates specific proteins for sustaining neuron growth through the injury core, and uses molecular guidance to steer nerve fibers towards their original targets.
When and where were the study’s findings published?
The findings were published in the September 22, 2023, edition of the journal Science.
Is there a plan to combine this gene therapy with other treatments?
Yes, the researchers anticipate that the gene therapy will work synergistically with electrical stimulation of the spinal cord to optimize the functional output of the regenerated fibers and the spinal cord below the injury.
What are the next steps for this research?
The next steps involve overcoming existing challenges to adapt this gene therapy for human application, including further development of the necessary technology for a more comprehensive solution to spinal cord injuries.
More about Spinal cord regeneration
- Publication in Science Journal
- .NeuroRestore Official Website
- Wyss Center for Bio and Neuroengineering
- EPFL Campus Biotech Facilities
- University of California, Los Angeles Neuroscience
- Harvard Medical School Neurobiology
- Gene Therapy in Neuroscience
- Spinal Cord Injury Research
- Single-cell Nuclear RNA Sequencing
- Electrical Stimulation in Spinal Cord Injury
