Metformin therapy in a transgenic mouse model of Huntington's disease

Neurosci Lett. 2007 Jan 10;411(2):98-103. doi: 10.1016/j.neulet.2006.10.039. Epub 2006 Nov 15.


Huntington's disease (HD) is a hereditary neurodegenerative disease that leads to striatal degeneration and a severe movement disorder. We used a transgenic mouse model of HD (the R6/2 line with approximately 150 glutamine repeats) to test a new therapy for this disease. We treated HD mice with metformin, a widely used anti-diabetes drug, in the drinking water (0, 2 or 5mg/ml) starting at 5 weeks of age. Metformin treatment significantly prolonged the survival time of male HD mice at the 2mg/ml dose (20.1% increase in lifespan) without affecting fasting blood glucose levels. This dose of metformin also decreased hind limb clasping time in 11-week-old mice. The higher dose did not prolong survival, and neither dose of metformin was effective in female HD mice. Collectively, our results suggest that metformin may be worth further investigation in additional HD models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Age Factors
  • Animals
  • Behavior, Animal
  • Blood Glucose / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Glutamine / genetics
  • Huntington Disease / drug therapy*
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Mice
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Multienzyme Complexes / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Sex Factors
  • Trinucleotide Repeats / genetics


  • Blood Glucose
  • Hypoglycemic Agents
  • Multienzyme Complexes
  • Glutamine
  • Metformin
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases