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

Science. 2018 Apr 6;360(6384):50-57. doi: 10.1126/science.aao2300.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / drug therapy*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Maleates / metabolism*
  • Maleates / pharmacology*
  • Maleates / therapeutic use
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Motor Cortex / drug effects*
  • Motor Cortex / injuries
  • Motor Cortex / physiopathology
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / drug effects
  • Neuroprotection*
  • Quality of Life
  • Receptors, AMPA / metabolism
  • Recovery of Function / drug effects*
  • Stroke / complications
  • Stroke / drug therapy
  • Thiophenes / metabolism*
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use

Substances

  • 1-(3-(2-(1-benzothiophen-5-yl) ethoxy) propyl)-3-azetidinol maleate
  • Intercellular Signaling Peptides and Proteins
  • Maleates
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • Thiophenes
  • collapsin response mediator protein-2