Gene Therapy Sparks Spinal Cord Regeneration

Paralysis reversal is achieved through spinal cord regeneration in cases of complete injuries. Researchers at NeuroRestore, Switzerland, reveal their groundbreaking gene therapy, which has successfully promoted nerve regrowth across spinal cord injuries in mice and guided nerves to reconnect with their original targets, leading to restored mobility ().

Meaningful recovery after severe injuries requires strategies that promote the regeneration of nerve fibers, but the requisite conditions for these strategies to successfully restore motor function have remained elusive.

Monoplegia
Monoplegia is the paralysis of one of the four limbs. It commonly affects the arms. It is mainly caused by cerebral palsy, but can be associated with other neurological conditions as well.

‘Complete spinal cord injury paralysis is reversed through regeneration as neuroscientists at NeuroRestore report a groundbreaking gene therapy, that successfully triggers nerve regrowth and reconnection with natural targets in mice, resulting in restored mobility. #Paralysis, #Regeneration ’

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“Five years ago, we demonstrated that nerve fibers can be regenerated across anatomically complete spinal cord injuries,” says Mark Anderson, a senior author of the study.

“But we also realized this wasn’t enough to restore motor function, as the new fibers failed to connect to the right places on the other side of the lesion.” Anderson is the director of Central Nervous System Regeneration at.NeuroRestore and a scientist at the Wyss Center for Bio and Neuroengineering.

NeuroRestore's Game-Changing Discovery Working in tandem with peers at UCLA and Harvard Medical School, the scientists used state-of-the-art equipment at EPFL’s Campus Biotech facilities in Geneva to run in-depth analyses and identity which type of neuron is involved in natural spinal-cord repair after partial spinal cord injury.

Paralysis
Paralysis is a condition where there is a loss of muscle function as well as sensory loss, which can occur due to damage to the brain or spinal cord. Paralysis treatment involves supportive care and rehabilitation.

“Our observations using single-cell nuclear RNA sequencing not only exposed the specific axons that must regenerate but also revealed that these axons must reconnect to their natural targets to restore motor function,” says Jordan Squair, the study’s first author.

The team’s findings appear in the September 2023 issue of Science. Their discovery informed the design of a multipronged gene therapy.

NeuroRestore's Game-Changing Discovery

The scientists activated growth programs in the identified neurons in mice to regenerate their nerve fibers, upregulated specific proteins to support the neurons’ growth through the lesion core, and administered guidance molecules to attract the regenerating nerve fibers to their natural targets below the injury.

Sleep Paralysis
Sleep paralysis is a temporary inability to move or speak or react. This occurs when the patient is trying to wake up or fall asleep.

“We were inspired by nature when we designed a therapeutic strategy that replicates the spinal cord repair mechanisms occurring spontaneously after partial injuries,” says Squair.

Mice with anatomically complete spinal cord injuries regained the ability to walk, exhibiting gait patterns that resembled those quantified in mice that resumed walking naturally after partial injuries.

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This observation revealed a previously unknown condition for regenerative therapies to be successful in restoring motor function after neurotrauma.

“We expect that our gene therapy will act synergistically with our other procedures involving electrical stimulation of the spinal cord,” says Grégoire Courtine, a senior author of the study who also heads.NeuroRestore together with Jocelyne Bloch.

“We believe a complete solution for treating spinal cord injury will require both approaches – gene therapy to regrow relevant nerve fibers, and spinal stimulation to maximize the ability of both these fibers and the spinal cord below the injury to produce movement.”

While many obstacles must still be overcome before this gene therapy can be applied in humans, scientists have taken the first steps towards developing the technology necessary to achieve this feat in the years to come.

Reference:

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region - (https://www.science.org/doi/10.1126/science.adi6412)

Source-Eurekalert