Diabetes Drug may Repair Injured Brains

Here’s a good brain teaser for a Wednesday.  What do an old diabetes drug, brain injury and Alzheimer’s Disease have in common?

Here’s some clues to help you solve the riddle.

(i)           Metformin is a widely used treatment for type II diabetes

(ii)          An increasing proportion of people with Alzheimer’s Disease also have diabetes

(iii)         Hyperinsulinemia (excess levels of insulin in the blood) may enhance the onset and progression of neurodegeneration

Have you solved it?  If so, congratulations!

If not, the answer, according to data just published in the journal Cell Stem Cell is that the former may hold the clue to treating the latter.

In other words, the study suggests that metformin, an anti-diabetes drug first discovered in the 1920’s, is able to help activate the mechanism that signals stem cells to generate brain cells.

Principal investigator, Freda Miller, a Professor from the Department of Molecular Genetics at the University of Toronto
says “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.”

The research involved laboratory experiments using both mouse and human brain stem cells, as well as learning and memory tests performed on live mice given the drug.

Miller and her colleagues 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.

In the key experiment, mice were forced to learn the position of a platform hidden under the surface of a water-filled maze and then asked rapidly to learn a new position.

Mice were injected with either metformin or saline for 38 days. On days 22 through 38, they learned the initial position of the platform, which provided an escape from the water-filled maze.  Then the platform was moved to the opposite side of the maze, and the animals were asked again to learn its position. In both tasks, the mice learned the platform positions with equivalent speed.

But when they were put back in the maze – this time with the platform removed – control mice spent more time searching for it in the original position, while the metformin-treated animals preferentially looked in the new region.

The implication  is that metformin helped the mice form their new memories of the second platform position. Further analysis showed that their enhanced ability was paralleled by an increase in the number of  neurons.

In a separate study researchers have shown that metformin can increase lifespan and delay the onset of cognitive impairment in a mouse model of Huntington’s disease.

Taken together, these findings raise the possibility that metformin’s ability to enhance neurogenesis might have a positive impact in some nervous system disorders.

Miller’s team is already planning a pilot study to test metformin in young patients with acquired brain damage, either as result of treating a childhood brain tumor or from a traumatic head injury.

We will report back to you with results, as they are published.

An aspirin-a-day keeps fat away

Aspirin is one of the most widely used medications in the world. A staggering 40,000 tons of it are consumed each year.

It’s also one of the oldest known medicines. First reports of its use date back to an Egyptian papyrus in 1543 BC. Hippocrates, the father of modern medicine, who lived sometime between 460 BC and 377 BC, left historical records describing the use of powder made from the bark and leaves of the willow tree to alleviate headaches, pains, and fevers. The active ingredient of this willow bark extract – salicylic acid.

In addition to its use as an anti-inflammatory pain reliever, aspirin is also used  as an anticoagulant / antiplatelet agent  to prevent strokes and heart attacks, and to stop coronary and carotid stents from blocking and to prevent deep vein thrombosis associated with long distance travel.

Aspirin has also been theorized to reduce cataract formation in diabetic patients and three studies published last month suggest that taking an aspirin every day may significantly reduce the risk of many cancers and prevent tumors from spreading.

Now, a group of researchers from Canada, Scotland and Australia have discovered that salicylate, the active ingredient in aspirin, directly increases the activity of the protein AMP-activated protein kinase (AMPK).  AMPK is a key player in regulating cell growth and metabolism.  It is considered a cellular fuel-gauge which can be switched on by exercise and the commonly used oral anti-diabetic medication metformin.

We’re finding this old dog of aspirin already knows new tricks,” says McMaster University associate professor of medicine Dr. Greg Steinberg.  The research shows that, in contrast to exercise or metformin which increase AMPK activity by altering the cells energy balance, the effects of salicylate depend on a single amino acid.

Salicylate increases fat burning and reduces liver fat in obese mice which does not occur in genetically modified mice lacking the beta1 subunit of AMPK.

These findings are important as a large clinical trial is currently underway testing whether salsalate (a well-tolerated aspirin derivative), can prevent Type 2 diabetes.  With many recent studies showing that metformin may be important for cancer prevention the authors’ study raise the interesting possibility that aspirin may also be working in a similar manner.

While further studies are needed, the prospect that this cheap, over-the-counter drug can increase fat burning while simultaneously preventing pain, clotting problems and possibly cancer, is probably one of the best health news stories of the year.