Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice

Exp Neurol. 2008 Oct;213(2):448-55. doi: 10.1016/j.expneurol.2008.07.017. Epub 2008 Jul 31.

Abstract

Edaravone is a free-radical scavenger, an agent being widely used for cerebral ischemia in Japan. To evaluate its efficacy for possible treatment of amyotrophic lateral sclerosis (ALS), we performed a randomized blind trial in ALS model mice. After identification of the clinical onset in each female G93A mutant SOD1 transgenic mouse, we intraperitoneally administered multiple doses of edaravone to the mice and observed their motor symptoms. We also counted the number of lumbar motoneurons, determined the 3-nitrotyrosine/tyrosine ratio, and evaluated the abnormal SOD1 aggregation in the spinal cord at the 10th day after the edaravone injection. Edaravone significantly slowed the motor decline of the transgenic mice. The remaining motoneurons were significantly preserved in the higher-dose edaravone-administered group, and the 3-nitrotyrosine/tyrosine ratios were reduced dose-dependently. Intriguingly, the area of abnormal SOD1 deposition in the spinal cord was significantly decreased in the higher-dose edaravone-administered group. Our results indicate that edaravone was effective to slow symptom progression and motor neuron degeneration in the ALS model mice. These favorable actions might be attributable to the yet unidentified mechanism responsible for reducing the deposition of mutant SOD1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / enzymology*
  • Animals
  • Antipyrine / administration & dosage
  • Antipyrine / analogs & derivatives*
  • Edaravone
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Skills / drug effects*
  • Motor Skills / physiology*
  • Motor Skills Disorders / drug therapy
  • Motor Skills Disorders / enzymology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • Time Factors

Substances

  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Edaravone
  • Antipyrine