Spinal cord injury (SCI)—a condition that leads to partial or complete paralysis—has a profound impact on millions of individuals globally. Despite recent advances in SCI treatment, restoring lost motor functions, such as hand movement, remains a significant challenge.
Now, in a new study published online in Brain Communications on March 13, 2025, a team led by Professor Takuya Takahashi from the Department of Physiology, Graduate School of Medicine at Yokohama City University, Japan, along with Dr. Yukio Nishimura, Neural Prosthetics Project from Tokyo Metropolitan Institute of Medical Science, Japan, reveal the potential of a promising oral drug candidate, edonerpic maleate, in accelerating recovery and improve motor function in non-human primates after SCI.
Prof. Takahashi explains, “Our previous study demonstrated the potential of this compound in accelerating motor function recovery after acute brain damage in rodents and non-human primates. These findings motivated us to evaluate its efficacy in recovery following SCI.”
The researchers used a non-human primate model to investigate the effects of edonerpic maleate on motor recovery following a partial cervical SCI. Initially, the monkeys were trained to retrieve food using their forelimbs as part of the experiment. After the injury which caused paralysis in their forelimbs, the monkeys showcased an inability to perform the task. However, by administering edonerpic maleate in conjunction with rehabilitation, the monkeys showed significant improvements in motor control, particularly in their ability to retrieve food with their affected hand.
This pioneering study focuses on the role of neural plasticity—the brain's ability to reorganize itself following injury to compensate for lost functions—in the recovery from paralysis. "Neural plasticity is a key mechanism by which the brain adapts to injury. Notably, our present study shows that edonerpic maleate can facilitate rehabilitation by promoting plastic changes in the brain, particularly in the motor cortex, to support recovery after SCI," explains Prof. Takahashi.
Their findings revealed that edonerpic maleate helps move α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors to the areas of the brain responsible for motor control. AMPA receptors are proteins found on nerve cells that play a crucial role in communication between neurons. They help transmit signals that are essential for muscle movement. By supporting this process, edonerpic maleate enhances the transmission of signals between the brain and muscles, which is vital for motor function. This signal transmission aids the rehabilitation process by strengthening the existing neural connections, thereby helping the brain regain control over movement.
Additionally, through intracortical microstimulation—a technique involving electrical stimulation of specific brain areas— the researchers mapped the motor cortex and found that edonerpic maleate administration expanded the cortical areas associated with distal upper limb muscles, which are essential for fine motor skills like grasping. This reorganization of cortical representation, along with improvements in motor function, suggested that edonerpic maleate helps the brain adapt to SCIs, facilitating faster recovery.
The rehabilitation effects of edonerpic maleate are also associated with the specific pathways that remain functional after SCI. This study emphasizes that, although new circuits are not formed through axonal regeneration (the regrowth of nerve fibers), the drug enhances the strength and efficiency of the residual pathways, particularly those involved in wrist and forelimb movements. This suggests that edonerpic maleate works by optimizing the existing neural networks to compensate for the injury.
"Although our study focused on the effects of edonerpic maleate in a non-human primate model, we believe these findings offer a promising path forward for human clinical applications," says Prof. Takahashi. He further adds, “We envision this novel drug being used in rehabilitation hospitals to enhance recovery from paralysis in patients with SCI worldwide.”
Overall, this research demonstrates that edonerpic maleate accelerates motor recovery after SCI by enhancing neural plasticity and supporting cortical reorganization. As this promising drug progresses toward clinical application, it holds the potential to alleviate the socioeconomic burden on individuals with SCIs by enhancing their recovery prospects. Furthermore, this research could promote innovation in the field of drug discovery, particularly in therapies focused on neuroplasticity.
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Reference
DOI: 10.1093/braincomms/fcaf036
About Yokohama City University
Located in the international city of Yokohama, Yokohama City University has 4 campuses, 5 undergraduate schools, 6 graduate schools, 2 affiliated research centers, and 2 affiliated hospitals that serve as the bases for education, research, and medical care.
Research emerging from Yokohama City University contributes to state-of-the-art technology with a global outlook. Aiming to contribute to the advancement of science and the global community, Yokohama City University also provides support to an array of global standard research programs.
About Professor Takuya Takahashi from Yokohama City University
Dr. Takuya Takahashi is currently a Professor at the Graduate School of Medicine, Yokohama City University, Japan. Professor Takuya Takahashi obtained his Ph.D. from Yale University in 2000. After conducting research as a Postdoctoral Fellow at Cold Spring Harbor Laboratory, he joined Yokohama City University as a Professor in 2006. His current interest lies in elucidating the molecular mechanisms underlying synaptic functions and their clinical applications, with a focus on AMPA receptors. He has published 50 major papers on these topics. He is currently a member of several academic societies, including the Japanese Society of Neurology, the Physiological Society of Japan, the Japanese Society for Neurochemistry, and the Japanese Society of Neuropsychopharmacology.
Funding information
This work was supported by FUJIFILM Corporation (T.T.), The Japan Society for the Promotion of Science KAKENHI P20H00549 (T.T.).
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