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Identification of a Novel Compound that Boosts the Rehabilitation Effects after Stroke
Clinical Trials to Be Conducted for a Novel Drug Approval
—Published in Science—
|April 4, 2018|
A research group led by Professor Takuya Takahashi, Department of Physiology, Yokohama City University Graduate School of Medicine and Toyama Chemical Co., Ltd. of the Fujifilm Group has identified a new drug candidate that boosts the rehabilitation effects after stroke in collaboration with the National Institute of Advanced Industrial Science and Technology and the National Institutes of Biomedical Innovation, Health, and Nutrition. Aiming for a novel drug approval, Toyama Chemical will conduct a clinical trial with post-stroke patients undergoing rehabilitation therapy.
Research Background and History
Content of the Research
First, the research group developed a method to evaluate forelimb function in mouse brain injury model, and revealed that motor function recovery was facilitated by the administration of edonerpic maleate in a rehabilitative training-dependent fashion. (Figure 1).
Furthermore, the research group used macaca monkeys to evaluate their human-like finger movements (to pinch an object). The research group induced brain hemorrhage in macaca monkey and demonstrated that the fine movements of the fingers is recovered by the administration of edonerpic maleate in combination with rehabilitation (Figure 2). The effect of current therapy with rehabilitation is often difficult to restore the fine finger movements which severely restrict patient’s quality of life.
These results demonstrated that edonerpic maleate is a promising drug that enhances rehabilitation effects in the recovery phase after a stroke.
*1 edonerpic: A compound developed by Toyama Chemical Co., Ltd., a member of the Fujifilm Group. Tolerability of the compound in healthy volunteers was verified in the clinical trials targeting Alzheimer’s disease.
*2 Synapse: A structure which conveys information from one neuron to the other neuron. Upon stimulation of one neuron, the information is mediated by neurotransmitter which is released from presynaptic terminal of the neuron and binds to its receptors in the other neuron, leading to the responses of postsynaptic neurons.
*3 AMPA receptor: One of the receptors for glutamate (a major neurotransmitter for the brain information processing). AMPA receptor forms ion channel in the synaptic membrane. Ion-influx through the receptor induced by the binding of glutamate contributes to postsynaptic response. Increase of AMPA receptors in the postsynaptic membrane results in the potentiation of postsynaptic response that is a central mechanism of information processing in the brain such as memory and learning.
*4 In vivo gene transfer: A method to express exogenous proteins by introducing genes into living animal. This research demonstrated the importance of AMPA receptor for motor function recovery after brain injury by virus-mediated expression of a protein that inhibits AMPA receptor function in the brains of mice.
*5 Electrophysiological analysis: A method to evaluate the communication between neurons by measuring the electric signals generated in neuron. By changing the experimental conditions, electric signals specific to AMPA receptors can be evaluated.
*6 CRMP2 (Collapsin-Response-Mediator-Protein2): A molecule that inhibits axonal growth. Recent research suggests its involvement in the neural plasticity.
*This research was conducted with grants from the Ministry of Education, Culture, Sports, Science and Technology “Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program,” the Japan Agency for Medical Research and Development (AMED) “Strategic Research Program for Brain Sciences (SRPBS),” and “Brain Mapping by Integrated Neurotechnologies for Disease Studies.”
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