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I Have Alzheimer’s or Another Dementia
Diabetes drug triggers neuron growth, potential to regenerate brain cells
TORONTO - A drug commonly used to control Type 2
diabetes can help trigger stem cells to produce new brain cells,
providing hope of a potential means to treat brain injuries and even
neurodegenerative diseases like Alzheimer's, researchers say.
study by scientists at Toronto's Hospital for Sick Children found the
drug metformin helps activate the mechanism that signals stem cells to
generate neurons and other brain cells.
"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,"
said principal investigator Freda Miller.
"This work is happening
against a background of a lot of excitement in the stem cell field about
the idea that since we now know that we have stem cells in many of our
adult tissues, then perhaps if we could figure out how to
pharmacologically tweak those stem cells, then perhaps we could help to
promote tissue repair," added Miller, a senior scientist at SickKids.
research, published online Thursday in the journal Cell Stem Cell,
involved lab-dish experiments using both mouse and human brain stem
cells, as well as learning and memory tests performed on live mice given
Researchers started by adding metformin to stem
cells from the brains of mice, then repeated the experiment with human
brain stem cells generated in the lab. In both cases, the stem cells
gave rise to new brain cells.
They then tested the drug in lab
mice and found that those given daily doses of metformin for two or
three weeks had increased brain cell growth and outperformed rodents not
given the drug in learning and memory tasks.
One standard test involves a water maze in which the mice must swim around until they locate a hidden platform.
the remarkable thing is the mice that got the metformin, what they
showed was increased flexibility in terms of the way they learned the
location of things," said Miller, explaining that the drug-treated mice
had a greater ability to learn and remember.
"If you then, for
example, moved the platform some place completely different, the
metformin-treated animals were remarkably good at just saying, 'OK,
things have changed' and learning the new thing and (were) much better
than the controls (untreated mice)."
Miller said it was
serendipity that led the team to conduct the study. About 18 months ago,
they found a pathway known as PKC-CBP that signalled embryonic neural
stem cells to make brain cells. At about the same time, some U.S.
collaborators at Johns Hopkins University found the same pathway was
activated by metformin in liver cells — the means by which the drug
controls glucose levels that go awry in diabetes.
Based on those findings, Miller's team thought metformin might activate the same pathway in neural stem cells.
love this story because it's a classic example of how very basic
research into how things work has led to a potential therapeutic
endpoint," she enthused.
One big bonus for researchers is that
metformin has been well-tested and long prescribed for a number of
diseases, including metabolic disorders in children. The drug also has
been shown to have anti-cancer properties.
"The advantage again is
that because metformin has been in people from seven until 107, we have
lots of safety data on it, we know exactly what kinds of doses, et
cetera, et cetera," she said. "So that's a really huge plus with moving
When it comes to progressive neurodegenerative diseases
such as Alzheimer's, Miller said there is a lot of excitement among
scientists about finding a drug that could recruit stem cells to produce
healthy neurons, "at least to give people just a bit longer healthier
cognition, if you will."
Metformin might be such a drug, but the
difficulty is that stem cells age and diminish as people get older, so
it's unclear whether there would be adequate numbers of healthy brain
stem cells to produce new neurons that would have a therapeutic benefit.
Still, it's a possible and worthwhile line of investigation, she said.
team is already in discussions with clinical colleagues about launching
a pilot study to test metformin in young patients with acquired brain
damage, either as result of treating a childhood brain tumour or from a
traumatic head injury.
Such a study would try to determine if
the drug could increase brain cell mass — using a functional MRI scan,
for instance — and measuring any improvement in cognition and behaviour.
If approved, Miller said a pilot study could begin within the next year or so.
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