Alzheimer's and insulin resistance

This is an old article from Time Health but it raises interesting points about insulin's effect on Alzheimer's and I thought it was worth sharing.

When the body refuses to make insulin, the condition is called type 1 diabetes; when the body mismanages the hormone, it's known as type 2. Now, scientists report new evidence linking insulin to a disorder of the brain: when the brain prevents the hormone from acting properly, the ensuing chemical imbalance may help trigger Alzheimer's disease. The correlation is so strong that some researchers are calling Alzheimer's disease "type 3" diabetes.

In the body, insulin helps convert food into cellular energy. But the brain has other uses for insulin, namely as a means to learn and make new memories. Here's how it works: At synapses, the spaces across which brain cells communicate and where memories are conceived, neurons reserve special parking spots just for insulin. When the hormone pulls in, a connection is made that enables new memories to form. Since new memory formation is one of the first things to go awry in people with early stages of the disease, this insulin-initiated process may hold the key to decoding the mystery of Alzheimer's.

In August, a team of scientists at Northwestern University were the first to show why the brain's "memory function" fails in the face of an insulin shortage. The group's prior research had already pinpointed the culprit: toxic proteins called amyloid beta-derived diffusible ligands (ADDLs, for short), which are known to pile up in the brains of people with Alzheimer's. Scientists also knew that Alzheimer's patients' brains have lower levels of insulin and are insulin resistant. But what the Northwestern team discovered is the molecular mechanism behind that resistance: when ADDLs bind to neurons at synapses, they obliterate the receptors that are normally reserved for insulin. Without those parking spaces on the brain cells' surface, insulin has no place to connect, and memory fails.

"We now understand that the function of insulin at those synapses is to modulate and influence the underlying cellular structure of memories," says William Klein, professor of neurobiology and physiology at Northwestern University and a co-author of the study published online by the FASEB Journal. "What we have here is a striking phenomenon that may ultimately explain why the brains of people with Alzheimer's disease are insulin resistant and how that ties into memory."

Researchers hope these findings will help shape future research in Alzheimer's therapy — perhaps in the development of drugs that can make brain cells' insulin receptors more responsive to the hormone, or in the application of type 2 diabetes drugs, which address insulin resistance, to Alzheimer's.

The notion that Alzheimer's disease might be a neuroendocrine disorder, akin to diabetes, isn't entirely new; it first showed up in the scientific literature roughly 20 years ago, but the idea petered out. In 2005, Suzanne la Monte, a neuropathologist at Brown University Medical School, revisited the idea. Based on two of her discoveries — that the brain makes its own insulin and that Alzheimer's disease depletes insulin — she coined the disease process "type 3" diabetes.

Still, referring to Alzheimer's disease as "type 3" diabetes is controversial, especially within the diabetes community. Alzheimer's disease is a complication of diabetes, not a unique form of the disease, says Dr. Sue Kirkman, vice president of clinical affairs for the American Diabetes Association. "Nevertheless," she says, "this is primarily a semantic argument."

The terminology aside, both diseases share many traits and risk factors, including high cholesterol, high blood pressure, and metabolic disorders. So, de la Monte sees the semantic "splitting of hairs" as a good thing. "People are arguing about small parts of the bigger story," she says. "At the end of the day, these conversations will help us to better understand both diabetes and Alzheimer's disease."

D Science

As a general rule I don’t repost stories about the latest diabetes “cure” that seem to be “almost” ready.  I mostly avoid doing this because I remember the first time I saw an article that claimed the researchers had cracked the code and just needed a few more dollars to cure us all. That first article came to my attention just weeks after Arden was diagnosed and it took me two days to realize that these “cures” have been pro ported to be just around the corner for decades. I believe that one of them will eventually break through but for me (or you) to emotionally chase each one of them, well that’s not a good idea. All of that doesn’t mean that I don’t follow along with what the scientific world is trying to do... Today, I’m reposting an article because this one seems a little different, just slightly more hopeful. It has no anti-rejection drugs that trade diabetes for cancer and it’s backed by a philanthropist with a strong personal connection and an eye for a good idea. In short this one seems doable to me. See what you think and comment if you’re so moved.

Fromhttp://m.xconomy.com/3376/show/9afa00bb7aaa31f4ea0ec98fd59537aa/

Posted by Arlene Weintraub on Friday Jun 24th at 4:00pm

What happens when a guy who got wealthy selling cars hands millions of dollars to a scientist and tells her how to spend it? Folks attending the American Diabetes Association conference starting today in San Diego are getting a hint of the answer to that question. Denise Faustman, director of the Massachusetts General Hospital (MGH) immunobiology laboratory is presenting two abstracts from a clinical trial funded by the Boston-based Iacocca Family Foundation, established by former Chrysler CEO Lee Iacocca to support research aimed at curing type 1 diabetes.

Faustman’s data shows that low doses of an 80-year-old vaccine temporarily reversed type 1 diabetes in Phase 1 human trial. The vaccine is called bacillus Calmette-Guerin (BCG). It was developed to prevent tuberculosis and is now available as a generic drug. BCG induces the immune system to make tumor-necrosis factor (TNF), which kills the T-cells that cause the pancreas to stop producing insulin.

Faustman’s team went to Iacocca’s foundation for funding after repeatedly having the door slammed in their faces by drug companies. The MGH scientists had plenty of animal studies showing that it was possible to regenerate the pancreas, and therefore restore insulin production in diabetes models. But when MGH went to the pharmaceutical industry looking for funding to research a pancreas-regenerating drug, “everyone said, ‘you’re reversing the disease. How are we going to make money?’” Faustman says.

So MGH spent years looking for a generic drug that would stimulate the production of TNF. Iacocca’s foundation supported much of that work, which involved drawing blood from thousands of diabetes patients and proving that they could use TNF to kill the bad T-cells. “One day, Mr. Iacocca looked at me and said, ‘Denise, when are you going to cure diabetes?’” Faustman recalls.

Iacocca instructed Faustman to show the technique worked in a mouse study, so it could eventually be tried in humans. “No one had ever reversed diabetes in a mouse,” she says. “Philanthropy can take risks. He made it clear it was his money and he wanted risky therapies done.” Then the foundation put $10 million toward the Phase 1 human trial. All told, Iacocca’s group is the largest single donor to Faustman’s research.

MGH’s Phase 1 study was designed to answer four key questions about BCG, Faustman says. “Does it kill the bad T-cells? Does it induce the good T-cells? Does it change the pancreas? Does it restore insulin secretion?” The data, she says, “shows positive responses in all four outcomes.”

One caveat, Faustman says, is that the drug produces a transient effect. That means it will have to be given in repeated intervals, perhaps every four to six weeks. Still, says Faustman, “this will be the first data showing that the pancreas can be turned back on.”

Iacocca launched his foundation in 1984 in honor of his late wife, Mary, who died of complications from type 1 diabetes. The foundation declined to comment for this story. But Kathryn Iacocca Hentz—president of the foundation and Lee’s daughter–said in a statement “These results are very meaningful to the Iacocca Family. We have supported this work since the mouse studies first showed the reversal of longstanding diabetes.”

The foundation has made a gift of undisclosed size to MGH to support the Phase 2 program, which MGH is now planning. The hospital has raised $8.5 million of the $25 million it will need to support the trial over the next three years. Though Faustman says they’ll need other partners to kick in additional funding, she’s certain they couldn’t have come this far without the help of the former Chrysler CEO. “You have to wonder how a guy who built cars knew what we needed to do,” she says. “But he knew what risks to take.”

New gel could speed wound healing

In this Wednesday Aug. 4, 2010 photo a demonstration of how wound-healing gel is used on a leg wound is seen at University College London. British scientists are about to begin a final phase of testing on a new gel that heals wounds up to five times as fast as normal treatment. The gel, named Nexagon, works by interrupting how cells communicate and prevents the production of a protein that blocks healing. That allows cells to move faster to the wound to begin healing it. Though it has only been tested on about 100 people so far, experts say if it proves successful, the gel could have a major impact on treating chronic wounds, like leg or diabetes ulcers, and even common scrapes or injuries from accidents. (AP Photo/Kirsty Wigglesworth)

LONDON — For three years, Connie McPherson had debilitating leg ulcers that were so painful she sometimes couldn't sleep. Despite repeated surgery, antibiotics, steroids and other treatments, nothing helped.

Then last year, she took part in a trial for a new gel aimed at chronic wounds.

"It was the answer to my prayers," said McPherson, 58, a real estate agent in Tulsa, Oklahoma. Within weeks, McPherson said the ulcer treated was completely healed. "I tried everything possible and this is the only thing that worked."

The gel used to treat McPherson was developed by a team led by David Becker, a professor of cell and developmental biology at University College London. The gel, named Nexagon, works by interrupting how cells communicate and prevents the production of a protein that blocks healing. That allows cells to move faster to the wound to begin healing it.

Though it has only been tested on about 100 people so far, experts say if it proves successful, the gel could have a major impact on treating chronic wounds, like leg or diabetes ulcers, and even common scrapes or injuries from accidents.

In most chronic wounds, Becker said there is an abnormal amount of a protein involved in inflammation.

To reduce its amount, Becker and colleagues made Nexagon from bits of DNA that can block the protein's production. "As that protein is turned off, cells move in to close the wound," Becker said. The gel is clear and has the consistency of toothpaste.

http://www.msnbc.msn.com/id/38671775/ns/technology_and_science-science/

TrialNet results for Cole

My son Cole (not a type I child) participates in a TrialNetNatural History study for the development of type I diabetes. It tests for “diabetes-related autoantibodies”.  Cole’s result was again negative, meaning that, “no diabetes related autoantibodies are present at this time” in Cole.  This doesn’t ensure anything in the future but it is wonderful news today to say the least.  Cole will be re-tested yearly until he is 18 yrs old.  

I would urge any siblings of a type I child to participate in TrialNet’s study. The information that they gather helps scientists understand so much about type I and can help a child that is at high risk to develop type I to stave of the disease.

That said, I received Cole’s letter today and opened it in the driveway.  I was choking back the tears of joy and guilt that I experience every time Cole gets this news.  I’m of course thrilled that Cole is not at an elevated risk of developing type I but at the same time I feel terrible for being happy while Arden suffers.  Anyway, back to it... I was choking back the tears when my neighbor came out of his house and began asking me a question, I was barely able to escape that conversation with my dignity when Arden’s nurse called to go over her lunch time insulin.  She too must have thought I was insane.  So to my neighbor and to Arden’s school nurse, I’m sorry if I cut our conversations short, I was trying not to cry.

And to a future Cole that I’ll one day let read this, I know we tell you that this test is to help Arden and other kids with type I but it’s also for you.  I’m sorry that I can never tell you your good news, I just don’t want you to worry.  This is one of the few times that I keep something from you.

That’s about as much transparency as I’ve got in me today...

To the rest of you, be transparent, test in public, your openness will grow understanding and I believe, quicken the path to a cure.

Nanovaccine helped mice overcome type 1 diabetes

CHICAGO (Reuters) - An experimental vaccine containing tiny molecules of an immune-system protein was able to reverse type 1 diabetes in mice, raising hope that it might work in people, Canadian researchers said on Thursday.

Type 1 diabetes is caused when certain white blood cells, called T cells, go haywire and begin attacking insulin-producing cells in the pancreas.

But not all T cells cause harm, said Dr. Pere Santamaria of the University of Calgary in Alberta, whose study appears in the journal Immunity.

"Essentially, there is an internal tug-of-war between aggressive T cells that want to cause the disease and weaker T cells that want to stop it from occurring," Santamaria said in a statement.

Santamaria's team wanted to find a way to counteract the harmful autoimmune response without compromising general immunity.

They developed a so-called nanovaccine -- particles many times smaller than a cell and coated with protein fragments specific to type 1 diabetes. These were bound to molecules that play a critical role in presenting these protein fragments to T cells.

When the team gave the vaccine to mice with an early form of type 1 diabetes, they found the vaccine slowed the progression of the disease. And in mice that had full-blown diabetes, the vaccine helped restore normal blood sugar levels.

The team said the vaccine appears to work by expanding the number of T cells working to fight off the attack of aggressive T cells that destroy the insulin-producing beta cells.

And they said the findings may lend clues about how to reverse other autoimmune diseases, such as multiple sclerosis or rheumatoid arthritis.

Teodora Staeva of the Juvenile Diabetes Research Foundation said in a statement the study was promising because the treatment worked only on the immune cells specifically focused on aggressively destroying beta cells, without compromising the rest of the immune system.

Type 1, formerly called juvenile diabetes, represents about 10 percent of the estimated 180 million cases of diabetes globally. Most diabetics have type 2, the kind linked with a rich diet and lack of exercise.

(Editing by Eric Walsh)

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The following are archived comments from this post. You can post new comments below.

Barbara (Julia's grandma)

Thank you, Scott, for putting this report about the vaccine on your web-site.   It gives us hope that someday there WILL be a cure for our precious girls and the many others with type 1 diabetes.

Tuesday, April 13, 2010 - 07:13 PM