Snuffing Out Alzheimer’s

confusedHot on the heels of Friday’s blog – Sniffing Out Alzheimer’s, British scientists just announced a major breakthrough that could, one day, result in a treatment for Alzheimer’s, Parkinson’s, Huntington’s and other neurodegenerative diseases.

In tests on mice, researchers from the toxicology unit of the Medical Research Council showed brain cell death from prion disease could be prevented.

Professor Roger Morris, from King’s College London, said: “This finding, I suspect, will be judged by history as a turning point in the search for medicines to control and prevent Alzheimer’s disease.”

It is rare to get cautious scientists keen to describe any study as a turning point in history, let alone a study in mice.

miceNot only is it is early science, a lot can go wrong between a drug for mice and a drug for humans and the only published data is for prion disease, not even Alzheimer’s.

So why the excitement?

It is the first time that any form of neurodegeneration has been completely halted, so it is a significant landmark. It shows that the process being targeted has serious potential.

The research team focused on the natural defense mechanisms built into brain cells. When a virus hijacks a brain cell it leads to a build-up of viral proteins. Cells respond by shutting down nearly all protein production in order to halt the virus’s spread.

neurodegenerative diseaseHowever, many neurodegenerative diseases involve the production of faulty or “misfolded” proteins. These activate the same defenses, but with more severe consequences. The misfolded proteins linger and the brain cells shut down protein production for so long that they eventually starve themselves to death.

This process, repeated in neurons throughout the brain, can destroy movement or memory or even kill, depending on the disease.  It  is thought to take place in many forms of neurodegeneration, so safely disrupting it could treat a wide range of diseases.

The researchers used a compound which prevented those defense mechanisms kicking in and in turn halted neurodegeneration.

The study showed mice with prion disease developed severe memory and movement problems. They died within 12 weeks. However, those given the compound showed no sign of brain tissue wasting away.

Lead researcher Professor Giovanna Mallucci says: “They were absolutely fine, it was extraordinary. What’s really exciting is a compound has completely prevented neurodegeneration and that’s a first. This isn’t the compound you would use in people, but it means we can do it and it’s a start.

She said the compound offered a “new pathway that may well give protective drugs” and the next step was for drug companies to develop a medicine for use in humans.

Side effects are an issue. The compound also acted on the pancreas, meaning the mice developed a mild form of diabetes and lost weight. Any human drug would need to act only on the brain.

David Allsop, professor of neuroscience at Lancaster University described the results as “very dramatic and highly encouraging.”

SRxA’s Word on Health agrees.  We look forward to seeing further research and how these findings could apply to diseases such as Alzheimer’s and Parkinson’s.

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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.