A complete spinal cord injury results in complete paralysis of all limbs and muscles below the site of injury. But now, EPFL scientists have demonstrated a new gene therapy in mice that can regenerate nerves and restore walking ability.
To use an outdated technological term, the spinal cord is the body's information highway. Messages between the brain and the rest of the body travel up the thick nerve bundles at incredible speeds. Therefore, damage to this pathway can be debilitating, leaving the patient without feeling or movement in the affected area.
Unsurprisingly, finding new ways to repair these injuries is a key area of research, with recent studies finding some success using implants that bypass the damaged area, nerve cell transplants, and proteins, molecules or compounds that help stimulate nerve regeneration. The EPFL team has previously tried to use gene therapy to regenerate nerve fibers, but with limited success.
"Five years ago, we demonstrated that nerve fibers could regenerate in anatomically intact spinal cord injuries," said Mark Anderson, senior author of the study. "But we also realized that this was not enough to restore motor function because the new fibers failed to connect to the correct location on the other side of the lesion."
To address this issue, researchers studied the natural repair process after partial injury to the spinal cord. 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 find the right target on the other side of the injury.
Through their analysis, researchers developed a new gene therapy that promotes neural reconnection in several ways at once. The therapy activates certain neuron growth programs to regenerate key nerve fibers; upregulates certain proteins that help neurons grow in damaged tissue; and adds molecules that guide these regenerated nerves to their target on the other side.
In tests on mice with complete spinal cord injuries, the team found that treated animals regained the ability to walk within months, with a gait similar to mice that recovered from partial injuries.
While much work remains to be done before this therapy can be used in humans, the team says it marks a crucial step toward the ultimate goal.
"We anticipate that our gene therapy will work synergistically with other procedures involving electrical stimulation of the spinal cord," said Grégoire Courtine, senior author of the study. "We believe that a complete solution for treating spinal cord injury will require two approaches - gene therapy to regrow the associated nerve fibers, and spinal cord stimulation to maximize the ability of those nerve fibers and the spinal cord beneath the injury to generate movement."
The research was published in the journal Science. The research team describes the work in the video below.