Metformin therapy in a transgenic mouse model of Huntington's disease.
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.
Ma
Thong C
TC
Division of Pharmacology, The Ohio State University, 412 Riffe Building, 496 West 12th Avenue, Columbus, OH 43210, USA.
Buescher
Jessica L
JL
Oatis
Benjamin
B
Funk
Jason A
JA
Nash
Andrew J
AJ
Carrier
Raeann L
RL
Hoyt
Kari R
KR
D055372:AMP-Activated Protein Kinases; D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005973:Glutamine / Q000235:genetics; D006816:Huntington Disease / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009097:Multienzyme Complexes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012737:Sex Factors; D018911:Trinucleotide Repeats / Q000235:genetics
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009097:Multienzyme Complexes; D005973:Glutamine; D008687:Metformin; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases