Damping Down Diabetes

SRxA’s Word on Health was very excited to learn of some amazing new research coming out of UC San Francisco.  Scientists there have identified a new way to manipulate the immune system and keep it from attacking the body’s own molecules in autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis.

More than 100 different autoimmune diseases have been discovered and they disproportionately affect women.  Of the 50 million Americans living and coping with autoimmune disease  more than 75% are women.  Autoimmune diseases are one of the top 10 leading causes of death of women under the age of 65 and are responsible for more than $100 billion in direct health care costs annually.   Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis and scleroderma by themselves account for > $50 billion.

But now, researchers, led by immunologist Mark Anderson, MD, PhD, a professor with the UCSF Diabetes Center, have discovered a type of immune cell called an extrathymic Aire-expressing cell (eTAC), which puts a damper on immune responses.  eTAC’s are a type of  dendritic cell – which make up less than 3% of the cells in the immune system. And, eTAC cells themselves account for a small fraction of all dendritic cells. eTACs reside in lymph nodes and spleen in both humans and mice.

In this study, Anderson’s team determined that eTAC’s can counteract the overactive immune response in autoimmune diseases and, in a mouse model of diabetes, can be manipulated to stop the destruction of the pancreas.

By displaying “self” molecules to T cells that target them, and permanently turning off these T cells, eTACs help the immune system tolerate the molecules naturally present within us.  “The mouse model we are working with involves using T cells that normally attack the islet cells of the pancreas, specifically by recognizing a molecule called chromagranin A that is present on islet cells,” Anderson said. “But if the eTACs can get to the T cells first and display chromagranin A, they can prevent T cells from attacking the islets.”

Anderson aims to exploit eTACs therapeutically by finding out how to grow them in large numbers outside the body. “We need to figure out how to grow a lot of these cells, to load them up with whatever molecule it is that we want to induce tolerance to, and then to load them back into a patient,” he said. “Such a strategy could help selectively shut down an unwanted immune response, such as the anti-islet immune response in type 1 diabetes.”

Dendritic cells work with T cells a bit like a sheriff working with a bloodhound.  But instead of presenting an article of clothing, dendritic cells present a specific molecule. If the molecule displayed by the dendritic cell matches the one the T cell was born to target, then that T cell would be activated to expand its numbers and to attack cells or tissues where the molecule is present.

When the interaction is between eTACs and T cells, however, the targeted T cell instead is turned off forever, and never seeks its molecular prey.

Given that the prevalence and incidence of and type 1 diabetes and other autoimmune diseases, such as Crohn’s, lupus and celiac disease are on the rise, this new research is extremely important, both from a public health and economic perspective.  With as many as three million Americans having type one diabetes and the incidence growing by more than 3% per year a cure is desperately needed.

Fighting Flu

Last night I participated in my annual healthcare lottery. Fortunately for my finances, this didn’t involve scratch cards, ticket stubs or wheel spinning of any kind, nor will it bring me great riches, a new car or a timeshare condo. Instead, if my gamble pays off, I might be spared the flu this winter season.

However, this may be one of the last years that I have to keep my fingers crossed that the vaccine might work.  In future years getting a flu shot may become a safe bet.

In a significant step against the disease that affects billions of people each year, scientists at Oxford University in the UK, just announced that they have successfully tested a universal flu vaccine that could work against all known strains of the illness.

This new vaccine targets a different part of the flu virus to traditional vaccines, meaning it does not need expensive reformulation and guess work  every year to try and match the most prevalent strains of the virus that are circulating the world.

The team, led by Dr Sarah Gilbert at the Jenner Institute, developed a vaccine that targets proteins inside the flu virus that are common across all strains, instead of those that sit on the virus’s external coat, which are liable to mutate.

If used widely, a universal flu vaccine could prevent pandemics, such as the swine flu outbreaks of recent years, and could even end the need for a seasonal flu jab.

A universal vaccine would save the time and money now needed to create vaccines to fight whatever particular virus has emerged in any given year.  The process of developing a seasonal vaccine takes at least four months and if the flu strain is highly pathogenic the delay means people get sick and die before the vaccine is ready.

“If we were using the same vaccine year in, year out, it would be more like vaccinating against other diseases like tetanus,” said Gilbert. “It would become a routine vaccination that would be manufactured and used all the time at a steady level. We wouldn’t have these sudden demands or shortages – all that would stop.”

While traditional vaccines prompt the body to create antibodies, Gilbert’s vaccine boosts the number of the body’s T-cells, another key part of the immune system which can identify and destroy cells that have been infected by a virus.

In her trial, Gilbert vaccinated 11 healthy volunteers and then infected them, along with 11 non-vaccinated volunteers, with a strain of flu virus.  She then monitored the volunteers’ symptoms twice a day.  Her results showed that the vaccine worked as planned.

“Fewer of the people who were vaccinated got flu than the people who weren’t vaccinated,” said Gilbert. “We did get an indication that the vaccine was protecting people, not only from the numbers of people who got flu but also from looking at their T-cells before we gave them flu. The people we vaccinated had T-cells that were more activated. The people we hadn’t vaccinated had T-cells as well but they were in a resting state so they would probably have taken longer to do anything. The volunteers we vaccinated had T-cells that were activated, primed and ready to kill. There were more T-cells in people we vaccinated and they were more activated.”

The trial proved two important things about the vaccine: First, it showed that it was safe; and second it proved that giving people flu virus in the presence of lots of T-cells induced by the vaccine was absolutely fine.

“What we’ll probably do is take the existing flu vaccine and mix in the new virus-vector vaccine, so you get both good antibodies and good T-cells. As well as giving you the antibodies for this season’s strain of flu, we’ll give you some T-cells that will cover this season, next year, and thereafter. It may not be 100% effective against all strains, but at least if there were a pandemic coming around, it would cover you for any strain.”

It is also believed that the vaccine could provide better protection against flu for older people. Traditional flu vaccines are effective in about 70-80% of young people, but only 30-40% of older people, because the older people’s immune systems are less efficient at making new antibodies.

The next step for the new vaccine is a larger scale trial comparing several thousand people who are given and not given the vaccine.

Although that means a commercial product is still some years away, this study represents some potentially very exciting findings not only for flu but possibly for other infectious diseases.

SRxA’s Word on Health looks forward to bringing you this news as it happens.

Unlocking the Mystery of Autoimmune Disease

A key feature of the immune system is its ability to discriminate between self and non-self.

When the mechanisms that prevent the immune system from attacking itself break down, it can result in autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, Crohn’s disease and diabetes.

Now researchers at Columbia University Medical Center claim they have not only found out why people with autoimmune diseases attack their own tissues and organs, but also how to correct the problem.

According to a study just published in The Journal of Clinical Investigation scientists have identified a defect in the T cell regulatory pathway which normally controls autoreactive T cells.  The majority of people with Type 1 diabetes who were tested were found to have a defect in CD8+ T cells that impacted their recognition of a common target structure known as HLA-E/Hsp60sp. More importantly, researchers were able to successfully correct the defect in-vitro.

“For decades, autoimmune diseases have been treated by reducing overall immune response. That’s been effective in extending life spans, but has been hard on the quality of life for many of those patients,” said lead researcher Hong Jiang, M.D. Ph.D.

Current therapies for treating autoimmune disease include steroids, which systemically suppress the immune system, resulting in multiple side effects, including weight gain and increased susceptibility to infections.  Therapies based on this new research are designed to selectively suppress immune responses to self-antigens without damaging the body’s normal anti-infection and anti-tumor responses.

This research is significant. The Columbia University scientists believe that this greater understanding of the defect could eventually lead to prevention of autoimmune diseases altogether.

SRxA’s Word on Health is keeping everything crossed.

Laughing on the lbs

We’ve all heard the expression “Fat and Happy”. While many in modern society might consider this an oxymoron, new research may provide a more scientific explanation.

Laughter is considered a positive stress (eustress) that involves complicated brain activities leading to a positive effect on health.

It was first suggested that laughter can benefit a person’s health as far back as the 1970s. Norman Cousins, a political journalist, diagnosed with an autoimmune disease, documented his use of laughter in treating himself into remission. He published his personal research results in the New England Journal of Medicine and is considered one of the original architects of mind-body medicine.

Now, researchers from Loma Linda, CA have picked up where Cousins left off.  Dr. Lee S. Berk, a preventive care specialist, and his colleagues have been studying the human body’s response to laughter and have found that it helps optimize many of the bodies functions. Berk’s group was the first to establish that laughter helps optimize the hormones in the endocrine system, including decreasing the levels of cortisol and epinephrine, which lead to stress reduction. They have also shown that laughter has a positive effect on modulating components of the immune system, including increased production of antibodies and activation of T-cells, especially Natural Killer cells.

Their studies have shown that repetitious “mirthful laughter,” which they call Laughercise©, enhances mood, decreases stress hormones, enhances immune system activity, lowers bad cholesterol (LDL) and systolic blood pressure, and raises good cholesterol (HDL).

Their latest research expands the role of laughter even further.

14 healthy volunteers were recruited to a three-week study to examine the effects that laughter and distress have on modulating the key hormones that control appetite.   During the cross-over study, each subject was required to watch a 20 minute video that was either upsetting or humorous in nature. Volunteers waited one week after watching the first video to eliminate its effect, then watched the opposite genre of video.

For a distressing video clip, the researchers had the volunteer subjects watch the tense first 20 minutes of the movie Saving Private Ryan. This highly emotional video clip is known to distress viewers substantially and equally.

For the eustress video, the researchers had each volunteer choose a 20-minute video clip from a variety of humorous options including stand-up comedians and movie comedies. Allowing the volunteers to “self-select” the eustress that most appealed to them guaranteed their maximum humor response.

During the study, researchers measured each subject’s blood pressure and the hormones-  leptin and ghrelin, which are both involved in appetite. What they found was that volunteers who watched the distressing video showed no statistically significant change in their appetite hormone levels during the 20-minutes they spent watching the video, while in contrast, the subjects who watched the humorous video had changes in blood pressure and also changes in the leptin and ghrelin levels. Specifically, the level of leptin decreased as the level of ghrelin increased, much like the acute effect of moderate physical exercise that is often associated with increased appetite.

The  research  may provide new insights and thus  potential options for patients who cannot use physical activity to normalize or enhance their appetite.  For example, many elderly patients often suffer from what is known as “wasting.”  They become depressed and, combined with a lack of physical activity, lose their appetite and jeopardize their health and well-being.  Based on Berk’s current research, these patients may be able to use Laughercise© as an alternative activity to regain their appetite.

Meanwhile, with pool season almost upon us SRxA’s Word on Health will be spending the summer watching Saving Private Ryan…again and again!