A new compound shows promise for improving motor function recovery for stroke patients in combination with rehabilitation therapy. Human clinical trials for a new drug are underway.
Japanese researchers have developed a new compound that enhanced motor function recovery after brain damage in animal tests, according to a study published in the journal Science.
The small-molecule compound, called edonerpic maleate, was developed by a research team led by Yokohama City University and Toyama Chemical Co., Ltd. in Japan. When administered to rodents and monkeys undergoing rehabilitation for brain damage, both groups of animals showed greater and faster recovery of motor function than those with just rehabilitation alone.
Toyama Chemical has already completed a clinical trial for the drug in healthy people, and plans to next conduct a clinical trial with stroke patients. The drug must complete three phases of successful trials before it can be approved as a medication.
More than 17 million people worldwide suffer from strokes each year. The majority of strokes block blood flow to the brain, which can lead to severe paralysis. Loss of function depends on the size and location of the affected area. Some available treatments are limited to the few hours following a stroke. Long-term treatment often involves different types of physical therapy, and motor function recovery varies from patient to patient.
In this new study, macaque monkeys receiving edonerpic maleate and undergoing physical therapy were able to pinch small foods with their fingers within a month of starting treatment. Recovery of such fine motor movements is often difficult for stroke patients.
Notably, the small-molecule compound shows positive results even when treatment started a month after the induction of brain damage - not just hours. This has the potential to boost recovery prospects for many stroke patients.
The compound appears to work in tandem with rehabilitation to enhance neural plasticity. Neural plasticity is the brain's ability to learn and adapt in response to experience. Brain cells affected by stroke cease to function normally within seconds of the trauma. However, the brain can create new pathways between neurons with external stimuli, in this case, physical rehabilitation.
Edonerpic maleate helps this process by facilitating the delivery of an important neurotransmitter receptor, called AMPA receptor, to the structures called synapses, which mediate information between neurons. The AMPA receptors are very important for signal transmission and information processing. They receive signals from glutamate, a major neurotransmitter, and help transmit the glutamate signal to the next neuron. By helping build up AMPA receptors at synapses in conjunction with rehabilitative training, edonerpic maleate helps increase the potential for a signal transmission and neuron response.
The researchers further determined that edonerpic maleate works by binding to an intracellular protein called collapsin-response-mediator-protein 2 (CRMP2), which is related to synaptic plasticity. Mice lacking CRMP2 protein did not show an increase in AMPA receptors nor recovery of motor function, even with edonerpic maleate, indicating that CRMP2 is critical for the compound to work.
The research was done in collaboration with Japan's National Institute of Advanced Industrial Science and Technology, and the National Institutes of Biomedical Innovation, Health, and Nutrition.
Abe, H. et al. "CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage." Science April 6, 2018 Vol. 360, Issue 6384, pp. 50-57 DOI: 10.1126/science.aao2300
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