Shared pathway could let diabetes drug treat Alzheimer’s

A new study in the journal Cell Stem Cell suggests that a very common diabetes drug, metformin, may also be useful in the treatment of neurodegenerative disease, like Alzheimer’s. By acting via the same pathway in neural stem cells as in liver cells, metformin was shown to stimulate the growth of neurons. This unexpected effect of the diabetes medication could have applications in repairing the brain after injury or disease.

A new study in the journal Cell Stem Cell suggests that a very common diabetes drug, metformin, may also be useful in the treatment of neurodegenerative disease, like Alzheimer’s. By acting via the same pathway in neural stem cells as in liver cells, metformin was shown to stimulate the growth of neurons. This unexpected effect of the diabetes medication could have applications in repairing the brain after injury or disease.

 

Therapies for Alzheimer’s disease, even today, are lacking. The neurodegenerative condition has proven so complex that researchers have not yet been able to unravel its mechanism; identifying targets for an anti-Alzheimer treatment has, therefore, not had enormous success. Now, a new potential treatment to stop or reverse the loss of neurons in the brain may have just come from an unexpected source: an already well known, widely used treatment for diabetes.

A team of researchers, led by neuroscientist Freda Miller of the Hospital for Sick Children in Toronto, connected the dots between earlier research of their own, and a diabetes research group’s study in liver cells. Previous work by Miller’s team had shown that a particular pathway, or molecular chain of events, was necessary for triggering stem cells in the brain to mature into differentiated neurons. The same pathway, aPKC-CBP, had also been shown to be activated in the liver by the anti-diabetes drug metformin. Dr. Miller’s team wondered if the treatment could activate the same important pathway in neural stem cells. If so, metformin might help to stimulate brain repair.

The study, published July 6 in Cell Stem Cell, found that both mouse and human neurons were indeed stimulated to grow in culture by metformin. The effect was also seen in the brains of mice given the medication, where more new neurons were produced. Interestingly, these mice also performed better on a maze test, indicating improvement in their spatial learning.

Metformin, a common diabetes drug, may encourage the growth of neurons in the brain. (Credit: Dr Jonathan Clarke. Wellcome Images. (Flickr/Rebecca-Lee))
Diabetes treatment Alzheimer's brain injury patients

Whether or not the treatment could also make people learn better, researchers hope metformin could be used to counteract neuron loss in the brain due to injury - the application Freda Miller's team plans to pursue - or  to neurodegenerative conditions. This potential application is all the more interesting since metformin is well characterized and known to be safe. (It is included on the World Health Organization’s List of Essential Medicines.) In the past, there were already signs that Alzheimer’s patients taking metformin for their diabetes experienced some positive effects on their brain disease, as well. Until now, though, doctors believed they were benefiting simply from better general health due to better diabetes control. If metformin proves to be useful in both diabetes and neurodegenerative disease, it will also have served as another lesson in the importance of communication among scientists working even in seemingly unrelated fields. Earlier this year, the cancer drug bexarotene was also found to have a considerable effect in mice in reducing the symptoms of Alzheimer’s. Time will tell if these promising leads result in much-needed therapies for patients.

Find out more: “Common diabetes drug promotes development of brain stem cells”, SickKids press release http://www.sickkids.ca/AboutSickKids/Newsroom/Past-News/2012/SickKids-researchers-suggest-metformin-helps-produce-new-brain-cells-enhance-memory.html

"Treatments for Alzheimer's Disease", Alzheimer's Association http://www.alz.org/alzheimers_disease_treatments.asp