Edonerpic maleate enhances functional recovery from spinal cord injury with cortical reorganization in non-human primates.

While spinal cord injury (SCI) aggravates the quality of life in humans by severe paralysis, clinical intervention to promote functional recovery from SCI is limited. We recently identified a small compound, edonerpic maleate (edonerpic MA), which accelerates training-dependent motor functional recovery from brain damage in rodents (cryo-genic cortical injury) and non-human primates (internal capsule haemorrhage) by the facilitation of experience-dependent synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the present study, we investigated whether edonerpic MA accelerates functional recovery after SCI in non-human primates. Six adult monkeys (Macaca fuscata) received a unilateral SCI between the C6 and C7 segment. After the SCI, upper limb motor function was immediately impaired and the animals were assigned to receive vehicle (n = 3) or 3 mg/kg/day edonerpic maleate (n = 3) by intramuscular injection for 2 months. The rehabilitative training and evaluation of behaviour using the slit task were performed 5 days a week for 2 months after SCI. The edonerpic MA-treated group showed significantly improved grasping movements than the control group. After recovery reached a plateau, we examined the somatotopic map of the contralesional primary motor cortex (M1) using intracortical microstimulation. The motor representation of wrist territory at contralesional M1 was larger in the edonerpic MA-treated group than in the control group. We concluded that edonerpic MA accelerates the recovery of grasping movements after SCI, accompanied by cortical somatotopic reorganization. Since edonerpic MA enhances recovery from damage in the central nervous system at multiple levels, treatment with edonerpic MA combined with rehabilitative training may represent a novel therapy for not only stroke but also for SCI.