On July 19,Cell published Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations. The studies have shown that when administered systemically, a small molecule compound activates these neural circuits in paralyzed mice, thereby restoring their ability to walk.

The researchers injected the CLP290 compound intraperitoneally into paralyzed mice with spinal cord injuries. Each group of mice received treatment for 8 to 10 weeks. The results showed that the paralyzed mice restores stepping ability after four to five weeks of treatment. Electromyography recordings showed that the two groups of related hind limb muscles actively moved in the paralyzed mice. After two weeks of stopping treatment, the walking scores of these mice were still higher than those of the control group.

These neurons produced a significant decrease in KCC2 after spinal cord injury. CLP290 is capable of activating the KCC2 protein in the cell membrane, enabling inhibitory neurons to again receive inhibitory signals from the brain. This causes the spinal circuit to turn to excitation, making it more sensitive to input signals from the brain. This has the effect of reviving the spinal cord circuit that loses its function due to spinal cord injury. A KCC2 agonist restores stepping ability in paralyzed mice and can be combined with epidural electrical stimulation to maximize the patient's function after suffering from spinal cord injury.

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