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Diabetes drug triggers neuron growth, potential to regenerate brain cells
Posted: Friday, July 6, 2012 2:07 PM
Joined: 5/7/2012
Posts: 97

Diabetes drug triggers neuron growth, potential to regenerate brain cells: study

Principal investigator Dr.Freda Miller is shown in an undated handout image.Canadian researchers have found that a drug widely used to treat Type 2 diabetes can help trigger the mechanism that signals stem cells to become brain cells.THE CANADIAN PRESS/HO - Hospital for Sick Children
Principal investigator Dr.Freda Miller is shown in an undated handout image.Canadian researchers have found that a drug widely used to treat Type 2 diabetes can help trigger the mechanism that signals stem cells to become brain cells.THE CANADIAN PRESS/HO - Hospital for Sick Children

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.

A 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.

The 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 the drug.

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.

"And 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.

"I 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 forward."

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.

Miller's 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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Lane Simonian
Posted: Friday, July 6, 2012 8:39 PM
Joined: 12/12/2011
Posts: 4845

Thank you for posting the entire article.  Only two types of neurons can be regenerated--olfactory neurons and neurons in the hippocampus.  These are the two types of neurons damaged in Alzheimer's disease.  In essence, one does not need stem cells to treat Alzheimer's disease because the neurons can potentially be regenerated naturally. 


The substance which regenerates neurons is known as brain derived neurotrophic factor.  It's expression is tied to beta adrenergic receptor activation.  Once again peroxynitrites--the main culprit in Alzheimer's disease--takes hydrogen away from this receptor inactivating it.  Thus neurons killed by the disease cannot be regenerated unless beta-adrenergic receptor activity is restored. 


The beta-adrenergic receptor can be re-activated by compounds that can donate hydrogen back to it (just like mood, short-term memory, alertness, social recognition, sleep, and smell can be restored by adding hydrogen back to the receptors that release neurotransmitters involved in each).   


Eugenol which is found in the essential oils most effective in treating Alzheimer's disease (such as bay laurel, clove, holy basil, coriander, and rosemary) will act just like the drug described in this article (metformin) except likely better because it can be directly inhaled into the hippocampus through aromatherapy and is probably a better hydrogen donor.  Plus one does not have to wait years for it to be tested and approved (as an aside type 2 diabetes is also caused by peroxynitrites so it makes sense that certain drugs or natural compounds such as cinnamon that are used to treat diabetes may also have an effect on Alzheimer's disease). 


Compare the effects of eugenol with metformin. 


Eugenol inhibits Aβ-induced excessive influx of calcium ion into neurons that causes neuronal death. Moreover, eugenol possesses an antidepressant-like activity. Eugenol, like other antidepressants, increases expression of brain-derived neurotrophic factor (BDNF) gene in the hippocampus, which is necessary for an antidepressant to exhibit its activity. Furthermore, eugenol inhibits monoamine oxidase A (MAO-A) and may restore monoamines that are decreased in the brain of patients with depression. Thus, eugenol can be a good medicine for AD and depression. Here we suggest that eugenol and its analogs can be used also for other diseases of the central nervous system (CNS) including Parkinson's disease (PD). This article reviews the previous investigations concerning effects of eugenol including its analogs on the CNS and describes perspectives of this highly potential compound. 


Almost all the damage done by peroxynitrites in Alzheimer's disease can be at least partially reversed no matter how far advanced the disease is. 

Rosemary for Alzheimer's treatment  


My mother is in the final stages of Alzheimer's and was given a rough estimate of only 6 more months of life back in November. As is very common, her condition can change from day to day but still in a general direction for the worse. She reached the point where, if she was even awake at all, she couldn't communicate anymore and hardly showed the sign of being aware of my presence. I've been using alternative medicine for a few years now to treat my depression, anxiety, and also for general health. I've since discovered the overlooked value of the herb Rosemary and now use it to treat the symptoms of my depression. I've also noticed better clarity of thought along with an improved short term memory. I was able to get the doctor's permission to give this herb to my mother and we figured at least it couldn't hurt. Much to my surprise, there's been a noticable change. There have been quite a few day now where my mom has been more focused and alert than she's been in a long time. I even got some news from one of her nurses who said my mother had a brief conversation with her. Its been at least a year or two since I can remember anything like that. This change has also been noticed by others on the nursing staff as well as her doctor, who is very surprised. Now I'm not suggesting this is any kind of a "cure" for Alzheimer's but the improvement in my mother's condition is something to be said about Rosemary and it's given me some more quality time with her that I thought had been thing of the past.........Gary
The answer is out there for the taking, but the problem is that no one in the scientific community or in Alzheimer's organizations appear ready to take it, biding their time for the next multi-billion dollar drug.