Using targeted gene therapy, mice who were entirely paralyzed can now walk

Tragically, absolute paralysis of all limbs and muscles below the lesion site follows a complete spinal cord injury. However, EPFL researchers have recently shown in mice that a novel gene treatment may rebuild nerves and regain the ability to walk.

To borrow an out-of-date technical phrase, the spinal cord serves as the body's information superhighway. Messages move up the dense network of nerves there at extraordinarily fast rates between the brain and every other area of the body. Damage to this conduit can be crippling as a result, causing patients to lose feeling and motion in the affected areas.

It should come as no surprise that one of the main areas of research is finding novel ways to repair these injuries. Recent studies have found some success with implants that bypass the wounded area, nerve cell transplants, and proteins, molecules, or other substances that help stimulate nerve regrowth. Using gene therapy, the EPFL team had previously attempted to restore nerve fibers with some degree of success.

Mark Anderson, the study's principal author, said: "Five years ago, we showed that nerve fibers can regenerate across anatomically complete spinal cord injuries." However, since the new fibers failed to attach to the proper locations on the other side of the lesion, we also learned that this was insufficient to restore motor function.

The researchers investigated how the body naturally repairs itself after a partial spinal cord injury to address the problem. The scientists used a method known as single-cell nuclear RNA sequencing to pinpoint the precise axons that must be repaired in order to restore motor function as well as how to locate the proper target on the other side of the injury.

From this approach, the researchers created a novel gene treatment that stimulates neuronal reconnection in multiple ways at once. In order to regenerate the important nerve fibers, the therapy turns on growth programs in a subset of neurons, upregulates a subset of proteins that aid in the growth of the neurons through the injured tissue, and adds molecules that direct the newly formed nerves to their destinations on the other side.

In experiments on mice with total spinal cord lesions, the scientists discovered that the treated animals regained mobility within months and eventually developed a gait like that of mice who had recovered from partial lesions.

Although there is still much to be done before this type of therapy may be used on humans, the team claims that it is an important step in the right direction.

According to Grégoire Courtine, senior author of the study, "We anticipate that our gene therapy will act synergistically with our other procedures involving electrical stimulation of the spinal cord." "We believe that a complete treatment for spinal cord injury will require both approaches: spinal stimulation to maximize the ability of both these fibers and the spinal cord below the injury to produce movement, and gene therapy to regrow relevant nerve cells."