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.

Feeling Fruity?

I’m sure all of our readers are familiar with the old saying, “An apple a day keeps the doctor away.”

Which, of course, got us musing, what about other fruit?  Well, it turns out that “An orange a day may keep strokes away!”  At least, it seems, for women.

According to a study just published in Stroke eating high amounts of citrus fruit, such as oranges and grapefruit, reduces the risk of ischemic stroke by 19%.

Researchers say the key to the reduced risk is a certain flavinoid found in citrus – flavonones. Citrus fruits and juices are the main dietary source of flavanones.

The findings were part of the Nurses’ Health Study, which included nearly 70,000 women who were followed for 14 years and reported on their dietary intake every four years.

While the risk of stroke was lower in those who ate citrus fruit, not all of the women’s flavonoid consumption came from citrus fruit. Flavonoids are also found in other types of fruit, vegetables, tea, and best news of all…dark chocolate and red wine.

This study confirms a previous findings that vitamin C and potassium, both of which are found in citrus fruits can protect against  heart disease, ischemic stroke and intracerebral hemorrhage.

Although some experts say that further prospective studies are needed to confirm these associations, we know what we’ll be putting in our shopping carts this week.

Stemming the Damage from Stroke?

UK based stem cell technology company ReNeuron announced this week that it has treated its first patient in the Phase I PISCES (Pilot Investigation of Stem Cells in Stroke) study.

The trial is designed to recruit a total of 12 men (> 60 years of age). Participants will receive a direct injection of ReN001 cells into the affected brain region between six and 24 months following their stroke. While the study will primarily evaluate the safety of the stem cells, a number of efficacy measures will also be evaluated over two years of follow-up.

The first patient was treated with the stem cells at the Institute of Neurological Sciences, Southern General Hospital, in Glasgow, Scotland; and was safely discharged two days after the straightforward neuro-surgical procedure. Southern General is one of Europe’s most innovative and well-recognized stroke treatment centers and is perhaps best known as the place where the Glasgow Coma Scale was developed.

Assuming a satisfactory independent Data Safety Monitoring Board review of the first patient’s progress in December 2011, the additional patients will be treated shortly thereafter. Subject to satisfactory safety data ReNeuron intends to pursue an accelerated clinical development pathway with ReN001, focusing on particular stroke patient groups who are expected to most benefit from the therapy.

Principal investigator Professor Keith Muir suggested that “if the therapy works it may allow new nerve cells to grow or regeneration of existing cells and actual recovery of function in patients who would not otherwise be able to regain function.”

Stroke is the third largest cause of death and the single largest cause of adult disability in the developed world.  It occurs when blood flow leading to, or in, the brain is blocked (ischemic stroke) or a blood vessel in the brain ruptures (hemorrhagic stroke). This results in damage to the nerve cells in the brain and a loss of bodily functions.

Stroke is the single largest cause of adult disability in the developed world. Over 700,000 people suffer a stroke each year in the US, of which, approximately 80% are ischemic in nature.

In the US, the annual direct and indirect costs of stroke are estimated to be in excess of $50 billion.

The type of stroke treatment a patient should receive depends on the stage of disease:

• Prevention – treatments to prevent a first or recurrent stroke are based on treating associated risk factors, e.g. high cholesterol, smoking and diabetes
• Immediately after the stroke – treatments attempt to arrest a stroke whilst it is happening by dissolving the blood clot that has caused the infarct
• Post stroke rehabilitation – aims to improve both functional and cognitive recovery in the patient weeks or months after the event.

ReN001 stem cell therapy seeks initially to target ischemic stroke patients in the third stage.  These patients constitute approximately one half of stroke survivors.

SRxA’s Word on Health will be following this story and will bring you updates as they happen.