A new study has revealed the potential of a promising oral drug candidate, edonerpic maleate, in accelerating recovery and improve motor function in non-human primates after spinal cord injury (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,” said professor Takahashi from Yokohama City University Graduate School of Medicine, Japan.
The 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 reorganisation 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 emphasises that, although new circuits are not formed through axonal regeneration (the regrowth of nerve fibres), 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 optimising 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,” said Takahashi.
“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.
