Research Article

CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage

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Science  06 Apr 2018:
Vol. 360, Issue 6384, pp. 50-57
DOI: 10.1126/science.aao2300

A small molecule for stroke therapy

Better therapies for motor impairments after stroke are greatly needed. In mice and nonhuman primates, Abe et al. found that edonerpic maleate enhanced synaptic plasticity and functional recovery after a traumatic insult to the brain (see the Perspective by Rumpel). This recovery of motor function was accompanied by functional reorganization of the cortex.
Science, this issue p. 50; see also p. 30

Abstract

Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.
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