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Diabetes Drug Could Rebuild Brains

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Dr. Cindi Morshead

For half a century, a drug called metformin has been making life better for people suffering from Type II diabetes. Now, Canadian researchers are finding that it could also offer remarkable benefits for something completely different. There is evidence that metformin can help an injured brain repair itself.

"It's very exciting," said Dr. Cindi Morshead, who is leading a research project at the University of Toronto that is partially funded by the Ontario Brain Institute.

Dr. Morshead and her team have seen extraordinary results, with the tantalizing prospect that metformin could stimulate the brain to regenerate damaged cells.

Her project builds on earlier work from another University of Toronto researcher, Dr. Freda Miller. In results published in 2012, Dr. Miller found that metformin encouraged the growth of new neurons in the brains of mice. They were being created in the hippocampus, the region where memory is stored. The animals also seemed better able to perform certain tasks--in effect, they appeared to be smarter after the metformin treatments.

The results gave Dr. Morshead an idea.

"The next question was: if it has this potential, could we use it to regenerate the brain?" she said in an interview.

Her team simulated a stroke in 9 day old mice, attempting to mimic the kind of injury that is thought to cause cerebral palsy in human beings. The mice showed the impact, with impaired movement and cognition.

The researchers administered metformin, either through the mother's milk or injections, and the results were striking. After a mere 7 days of metformin treatments, the mice were moving better. After about 4 weeks, there was also evidence of improvements in cognition.

The mice's neural stem cells had been pre-marked to appear fluorescent green. After the treatment, the researchers found more green: the cells had divided, made copies of themselves and migrated throughout the brain tissues.

The findings raise hope that metformin could help people with cerebral palsy. Traditionally they have been treated with rehabilitation, but the results have always been limited. Clinical trials still need to be done, and there are unanswered questions about whether metformin needs to be administered shortly after the injury, or whether it could still be effective long afterwards. But if a drug could rebuild damaged brain cells in people with CP, it would be a dramatic advancement.

And that is not all.

Researchers at the Hospital for Sick Children are exploring metformin's possibilities for treating a different acquired brain injury. Children who develop medulloblastoma, a form of brain cancer, are usually treated through surgery to remove the tumour, coupled with chemotherapy and/or radiation.

Although the survival rates are relatively good, the treatments often leave the patients with long term cognitive and motor impairments.

The Sick Kids study will investigate whether metformin could help these young people in the same way that it seemed to be improving the condition of Dr. Morshead's mice.

Aside from the potential therapeutic benefits, finding new uses for an old drug means bypassing a lengthy approval process. Metformin has been used for decades and its safety already proven. Brand new pharmaceuticals can take years to go through all the requisite studies.

"In theory it's a quick way to get it to the clinic and then get to people with cerebral palsy," said Dr. Morshead.

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