A specific inhibitor of janus kinase-3 increases survival in a transgenic mouse model of amyotrophic lateral sclerosis

Biochem Biophys Res Commun. 2000 Jan 7;267(1):22-5. doi: 10.1006/bbrc.1999.1905.


Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder involving the motor neurons of cortex, brain stem, and spinal cord. About 10% of all ALS patients are familial cases (FALS), of which 20% have mutations in the Cu, Zn-superoxide dismutase (SOD1) gene. The murine model for FALS, which overexpresses a FALS variant of the SOD1 gene, exhibits progressive limbic paralysis followed by death. Treatment of FALS mice with WHI-P131, a specific inhibitor of Janus kinase 3 (JAK3), increased survival by more than two months, suggesting that specific inhibitors of JAK3 may be useful in the treatment of human ALS. These results uniquely establish JAK3 as a novel molecular target for the treatment of FALS.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Disease Models, Animal
  • Enzyme Inhibitors / therapeutic use*
  • Genetic Variation
  • Genistein / pharmacology
  • Genistein / therapeutic use*
  • Heterozygote
  • Humans
  • Janus Kinase 3
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Motor Neuron Disease / drug therapy*
  • Motor Neuron Disease / genetics*
  • Neuroprotective Agents / therapeutic use*
  • Paralysis
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Superoxide Dismutase / genetics*


  • Antioxidants
  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Quinazolines
  • WHI P131
  • Genistein
  • Superoxide Dismutase
  • Protein-Tyrosine Kinases
  • JAK3 protein, human
  • Jak3 protein, mouse
  • Janus Kinase 3