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"... The EPFL team had previously managed to regenerate nerve fibers using gene therapy, but had limited success.
“Five years ago, we demonstrated that nerve fibers can be regenerated across anatomically complete spinal cord injuries,” ...
To fix the issue, the researchers studied the natural repair processes that take place after a partial spinal cord injury. Using a technique called single-cell nuclear RNA sequencing, the team identified the specific axons that need to be repaired to restore motor function, and how they can find the right target on the other side of the injury.
From this analysis, the researchers developed a new gene therapy that works in a few ways at once to boost the reconnection of nerves. The therapy activates growth programs in certain neurons to regenerate the key nerve fibers, upregulates certain proteins that help the neurons grow through the damaged tissue, and added molecules that guide those regenerating nerves to their targets on the other side.
In tests in mice with complete spinal cord injuries, the team found that the treated animals regained the ability to walk in a matter of months, ending up with a gait similar to those of mice that had recovered from a partial injury. ..."
From the editor's summary and abstract:
"Editor’s summary
Although several experimental approaches have shown positive results in axonal regeneration after spinal cord injury (SCI), complete recovery of motor functions remains an elusive target. Squair et al. hypothesized that restoration of complete axonal projection of a selected neuronal population to their natural target could promote better functional recovery. After using single-cell RNA sequencing to identify the most promising neuronal population, the authors showed that promoting axonal growth and path guidance to their natural target in this population restored walking in mice after complete SCI. By contrast, broad axonal restoration across the lesion had no effect, suggesting that a more targeted approach is necessary for functional recovery after SCI. ...
Abstract
Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions."
Regeneration across complete spinal cord injuries reverses paralysis (primary news source) A complete spinal cord injury leads to irreversible paralysis. Scientists at .NeuroRestore report in Science that they have developed a gene therapy that was proven in mice to stimulate nerve regrowth across such injuries and guide nerves to reconnect to their natural targets below the injuries in order to restore motor function.
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