Common diabetes drug promotes development of brain stem cells
July 10, 2012
Metformin, a drug commonly used to treat Type II diabetes, can help trigger the pathway used to instruct stem cells in the brain to become nerve cells researchers at The Hospital for Sick Children (SickKids) have found.
Brain stem cells and the neural cells they generate play a role in the repair of the injured or degenerating brain. This study suggests a novel therapeutic approach to treating people with brain injuries or potentially even neurodegenerative diseases.
“If you could take stem cells that normally reside in our brains and somehow use drugs to recruit them into becoming appropriate neural cell types, then you may be able to promote repair and recovery in at least some of the many brain disorders and injuries for which we currently have no treatment,” says Dr. Freda Miller, Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto.
The researchers previously found a pathway known as PKC-CBP that signalled embryonic neural stem cells to make neurons. Around the same time, their collaborators from Johns Hopkins Medicine found that the same pathway was activated by metformin in liver cells; this was how metformin controlled glucose levels. On the basis of these findings, Miller’s team thought that perhaps metformin would activate the same pathway in neural stem cells, and would provide a way to enhance neural stem cell function in the brain.
Their hunch turned out to be correct. The researchers found metformin promoted differentiation of human and mouse neural stem cells in culture. In adult mice, metformin was found to increase the development of new neurons in the brain and when mice performed water maze tests, metformin was found to increase their ability to learn and remember.
Because metformin is already a commonly-used drug, clinical trials may not be very far off. “As a next step, we would be interested to see if individuals with acquired brain injury might benefit from taking metformin,” says Miller.
- Jing Wang, Denis Gallagher, Loren M. DeVito, Gonzalo I. Cancino, David Tsui, Ling He, Gordon M. Keller, Paul W. Frankland, David R. Kaplan, Freda D. Miller, Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation, Cell Stem Cell, 2012, DOI: 10.1016/j.stem.2012.03.016