Diabetes Drug: Another New Hope for Alzheimer’s?

I often worry about the time I spend on the computer researching and writing this blog. But I just joined my housemates in the rec room, intending to ride my exercise bike and watch TV with them. My housemates were watching one of the endless "amateur hour" talent shows. This one was called The Voice. I had wanted to ride the bike for about 15 minutes, but I had to leave after just five minutes. What mind-numbing crap!

Dementia is another chronic worry. If I am headed in that direction, I'd surely speed up the process if I spent my evenings watching shows like that.

I find internet research on health topics fascinating and mentally stimulating. Maybe it also helps slow down any drift toward dementia. In any event, it's a more enjoyable way to spend an evening. Even with a good TV show, I tend to doze off after 9 pm, which makes it more difficult to sleep later. But the interactive demands of internet research keep me alert for hours.

So many new breakthroughs are happening in medical research! New studies involving the brain are especially fascinating, particularly for someone with Parkinson's, a disease that has certainly been reducing dopamine-generating cells in my brain for years. New findings establish two principles. First, the adult brain continues to grow and develop throughout our lives. Second, brain development in adulthood is shaped mostly by external stimuli. These conclusions suggest we can conduct healthy "workouts" for our brains, just as we do for our bodies.

The exercise bike for my brain includes scanning the online Science Daily's Mind & Brain News. In its  September 14 edition,, I found a report on the promise of a new diabetes drug to treat Alzheimer’s.

Insulin and Brain Health

In this study on mice, scientists at the University of Ulster used an experimental drug called (Val8)GLP-1, which mimics the activity of the natural protein GLP-1 (glucagon-like polypetide-1). This protein helps regulate the body’s response to blood sugar – the reason it has been useful in treating type 2 diabetes.

We’ve known for a long time that type 2 diabetes is a risk factor for developing Alzheimer’s. Research has shown that insulin plays a role in memory formation. When amyloid structures attach to neurons, the neurotoxins cut off insulin receptors, eventually producing insulin resistance in the brain. Developing diabetes then creates denser amyloid accumulation, making neurons even more insulin resistant. It’s a vicious cycle, in which diabetes and memory impairment develop concurrently, from the same cause.

The University of Ulster study showed that (Val8)GLP-1:

• crossed the tricky blood-brain barrier without difficulty, 
• promoted growth of new cells in the brain’s hippocampus region, which plays a key role in consolidating memory, and 
• appeared to create no side effects at the doses tested. 

Said lead researcher Christian Hölscer:

We are really interested in the potential of diabetes drugs for protecting brain cells from damage and even promoting new brain cells to grow. This could have huge implications for diseases like Alzheimer's or Parkinson's, where brain cells are lost. It is very encouraging that the experimental drug we tested, (Val8)GLP-1, entered the brain and our work suggests that GLP-1 could be a really important target for boosting memory.

Of course, the reference to Parkinson’s is heartening to this PWP. Progress on one neurodegenerative condition, like AD, often carries implications for others, like PD.

Dr Simon Ridley, Head of Research at Alzheimer's Research UK offered the standard caveat: "We are pleased… that this experimental diabetes drug could also promote the growth of new brain cells. While we know losing brain cells is a key feature of Alzheimer's, there is a long way to go before we would know whether this drug could benefit people with the disease."

He added, "This research will help us understand the factors that keep nerve cells healthy, knowledge that could hold vital clues to tackling Alzheimer's.”

A Plethora of Alzheimer’s-Diabetes Links
Science Daily has regularly updated new developments in the growing connections between AD and PD. Here are just a few:

• April 17, 2009: Novel Mechanisms Might Causally Link Type-2 Diabetes To Alzheimer's Disease
• October 28, 2009: Does Diabetes Speed Up Memory Loss In Alzheimer's Disease?
• August 26, 2010: Insulin Resistance, Type 2 Diabetes May Be Linked to Plaques Associated With Alzheimer's Disease, Study Suggests
• October 13, 2010: Diabetes Gene Linked to Degeneration of Enzyme Involved in Alzheimer's Disease Onset and Progression

This was much more fun and interesting than watching The Voice!

Memory: Two Updates

At 83, I count my blessings that I am

• still living in my own house, 
• managing quite well on my own, 
• enjoying a pretty jam-packed retirement, 
• coping well with my various afflictions, and 
• feeling happy and contented most of the time

I've got two progressive diseases -- Parkinson's and prostate cancer -- but strangely enough I don't spend much time worrying about them. I worry more that the lousy short-term memory I've had most of my life is getting worse. Dementia – and its more acute cousin, Alzheimer’s – are my greatest fears.

Two articles about memory recently hit my inbox. One gave encouraging news about brain structure; the other focused on the role of genetics.

Brain Cells Don’t Keep Dying Off as We Age
Last month, a Johns Hopkins "Health Alert" reported that our brains do not experience a massive loss of cells as we get older, contrary to long-held beliefs. In fact, as science progresses, we learn more and more about the brain’s amazing plasticity – its ability to grow and change, and even “heal” itself.

Maybe most encouraging of all, there is considerable growth of new cells in the hippocampus, the part of the brain that consolidates our memories.

The article makes the point that our brains are organs, like our hearts and lungs. Brains are affected by the same things -- like diet and exercise -- that affect our other organs. While it may not be “news,” it’s good to read again that we have some measure of control over the quality and duration our memories, through the lifestyle choices we make.

What We Don’t Control: Genes
Another article was reported by Dr. Shari Barnett of ABC News. She told the story of Ralph Light, 94, an active gardener, living with his wife of 68 years, reader of two or three novels a week... and brother of four siblings who lived long, dementia-free lives.

Barnett reports on a study conducted by Mount Sinai School of Medicine, which examined 277 dementia-free male veterans, all 75 or older, to measure levels of C-reactive protein. Higher levels of this substance are associated with increased dementia risk. The question becomes: how have men with high levels of C-reactive protein – who also have no evidence of cognitive impairment – managed to develop some kind of “immunity” to dementia? The answer could have powerful implications in the quest for treatment, and even prevention, of Alzheimer's.

This study, and another similar follow-up investigation, included interviews with relatives of these mentally healthy vets with high C-reactive protein levels. Results were not surprising: the study subjects who were “resistant” to high C-reactive protein levels were 30% less likely to have relatives with dementia.

Yes, it's another validation that our DNA deals us a hand we’re stuck with. But we can still play it cleverly.

Dr. John Messmer, associate professor of family and community medicine at Penn State College of Medicine in Hershey, Pennsylvania, commented on the study:

Mr. Light's family likely has a good genetic profile plus a lifetime of physical activity and is not overweight or a smoker. And he is engaged in life. All the research being done on dementia may one day help us to understand it better, but for now, there are basic recommendations to reduce one's risk: do not use tobacco, maintain a strictly normal weight (BMI under 25), exercise regularly, eat a diet high in vegetables and fruits, stay engaged in the community.

Check, check, check, and check.

Alzheimer’s, Parkinson’s, and an Interview with Ted Dawson

This past Monday, I wrote about the exciting new trial underway involving an extended family in Colombia, South America. Many of them carry a genetic mutation that will cause early onset Alzheimer’s disease (AD) when they’re in their mid 40s. Researchers know in advance which family members carry the mutation, and their aim is to use a new drug therapy to PREVENT the disease before its devastating symptoms – to date irreversible – even begin. Yes, a new paradigm.

Today, I read an interview with Ted Dawson -- Professor of neurodegenerative diseases and Director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine -- in which he essentially said the same thing about his recent Parkinson’s disease (PD) research: “…for disease modifying therapy, we are treating patients too late. We really need to treat patients earlier.”

Since AD and PD are both neurodegenerative conditions, it’s not surprising that researchers occasionally travel along the same track… in this case trying to identify likely sufferers sooner in order to begin therapy – hopefully PREVENTIVE therapy – earlier. Once either disease appears, the most we can do – at this time, anyway – is treat the symptoms. Still, I am lucky we’ve come that far.

Of course, different challenges confront scientists working on the two diseases. So far, researchers seem to have a better chance of identifying healthy, but disease-prone candidates for Alzheimer’s studies -- at least in the condition’s early-onset variety -- than for PD. Those afflicted Colombian family members all carry the presenil 1 mutation, which researchers can identify in advance. If there’s a similar, scientific way to tag PD candidates long before symptoms appear, I’m not aware of it. Writes Dawson, “Despite genetic advances in our understanding of PD, it is primarily considered a sporadic disorder with no known cause. “

There’s another difference between the Colombian AD study and Dawson’s recent PD work. In that first case, study participants will receive the drug crenezumab, which researchers hope will prevent the accumulation of amyloid plaques. Dawson’s work involves drug therapy, but also includes induced pluripotent stem (IPS) cells, “teased” from skin cells. I’ve written about that particular technology before.

The brief interview with Dawson about his work with Parkinson’s is very interesting.

Alzheimer's: Inflammation, Pine Cones, Popcorn

The march of science to create a treatment for Alzheimer’s continues apace. Two new articles recently caught my eye.

Neuroinflammation as Culprit
As reported in the July 25 issue of The Journal of Neuroscience, a new drug may soon become available that treats a range of conditions – including Alzheimer’s, Parkinson’s, multiple sclerosis, and brain injuries – by reducing inflammation in the brain.

Unlike other recent therapies that target amyloid plaques and tangles – protein accumulations in the brain that typically indicate Alzheimer’s – the new drugs, including MW151 and MW189, are designed to improve neuro-function by reducing inflammation.

D. Martin Watterson, study co-author and molecular pharmacology and biological chemistry professor at Northwestern University Feinberg School of Medicine, reported that his university received patents for this new drug class, and licensed commercial development to a biotech company. Phase one of the clinical trials on humans – screening for safety – was recently completed.

Earlier, using rodent subjects, researchers found that the drugs prevented development of full-blown AD in mice that had been genetically-tweaked to develop the disease.

Additional information about the study can be found on this Northwestern University “NewsCenter” bulletin.

And Now… Pine Cones?

As reported in today’s issue of the UK's "Daily Mail" OnLine, a chemical found in pine cones and grape seeds may prevent the formation of tell-tale amyloid plaques in the brain, thereby preventing the development of Alzheimer’s. The new drug based on that naturally occuring compound is called NIC5-15.

The Humanetics Corporation – in concert with researchers from Mount Sinai School of Medicine – developed the drug, and completed phase one clinical trials on humans to verify its safety. Humanetics President and CEO Ronald Zenk said: “There is an urgent need for safe and effective disease modifying agents to lessen the debilitating symptoms of Alzheimer's disease. We are hopeful that NIC5-15 will satisfy that need.”

The company is now seeking several hundred AD sufferers in New York, to determine dosage levels that yield maximal benefit with minimal side effects.

Hmmm. I eat lots of grapes, but I'm not sure how to consume pine cones.

Postscript: Popcorn Lovers, Beware!
As a sidebar to the Daily Mail article about the new Alzheimer’s drug NIC5-15, there appeared the warning below:

An artificial ingredient that gives popcorn a buttery flavour has been linked to a key Alzheimer’s brain process. 

Researchers from the University of Minnesota tested the effect of the ingredient diacetyl (DA) in a lab at exposure levels common in food factories. 

They found DA increased the level of amyloid clumping - a hallmark of Alzheimer's disease. 

It also easily penetrated the “blood-brain-barrier”, which keeps many harmful substances from entering the brain. 

The team, led by Robert Vince, said considering how exposed industry workers were to DA “this study raises the troubling possibility of long-term neurological toxicity." 

Popcorn? Who knew?