Chinese Fungus a Potential Immunosuppressant to Treat MS

Saw an interesting article in the Wall Street Journal about a new drug being introduced by Novartis called fingolimod. The drug is used to suppress the immune system, treating some of the symptoms of multiple sclerosis. I'm generally not a big fan of immunosuppressants, but the article does suggest why many alternative therapies work.

The drug is based on a fungus known as "winter-insect-summer-plants". An excerpt describing the fungus:

Dr. Fujita says he reasoned that an even more powerful immunosuppressant chemical ought to be present in a group of Asian fungi known in Chinese and Japanese as "winter-insect-summer-plants." These fungi attack insects in the winter with their chemical arsenal. By summertime, the insect is dead and its corpse has been transformed into a vessel for the blooming fungus. Ironically, the same properties that make the chemical deadly in the insect world may also have a helpful side for people suffering from certain autoimmune diseases, in which an overactive immune-system response causes the body to attack its own cells.

There are many natural remedies used in Chinese and Japanese medicine, including herbs and fungus. Perhaps many of these work because they are immunosuppressive.

When Good Germs Go Bad - Friendly Bacteria Triggers Arthritis in Mice

Saw a really interesting article in Scientific American about a study regarding a link between a specific strain of bacteria and rheumatoid arthritis (RA) in mice. The study found that the introduction of a single type of bacteria could increase the amount of IL-17 (interleukin 17), a protein that signals the immune system to cause inflammation, in the mouse. The "friendly" bacteria that causes this accelerated the onset of arthritis in the mice. The mice were selected to already be genetically predisposed to having arthritis, so all mice in the study developed arthritis. But the mice that were given the bacteria developed RA much more quickly.

Why is this important? This could mean that exposure to even a single bacteria or virus could trigger an autoimmune reaction in genetically susceptible individuals. Here's an excerpt:

Mathis emphasized that one should not take away from these mouse studies "that mice or humans can 'catch' an autoimmune disease or arthritis," she says. She added that the better way to think about it is that individuals have varying degrees of genetic susceptibility, and when exposed to certain environmental factors may then go on to develop disease. "It's really an interaction between genetics and environment," Mathis says.

Crohn's Disease or Inflammatory Bowel Disease (IBD) may have a similar pattern to RA. It could also mean that there is a single bacteria or virus responsible for the disease. Or ... it could also mean that there are any number of bacteria or viruses that trigger the disease. Either way, it's a very study and reinforces previous theories and studies I've seen.

Prostaglandin D2 a potential treatment for Ulcerative Colitis

A recent study may suggest a new treatment for ulcerative colitis. The study, to be published in the journal Proceedings of the National Academy of Sciences, found that people with ulcerative colitis that have been in remission for a long time-period have higher levels of Prostaglandin D2 than those that don't. It's unclear whether the higher levels of the chemical are a result of being in remission or the cause of the remission, but the study is interesting nonetheless as it suggests follow-on research.

FDA requires cancer warning on TNF blockers (old news)

I've thought for a while that TNF blockers and other immunosuppressive drugs may actually be counterproductive in the long-run in treating Crohn's Disease and IBD. The point of TNF-alpha in the immune system is to promote the fight against tumors (TNF = tumor necrosis factor). What happens if you suppress that immune response? Your body may be missing tumors that it should be fighting. A recent article prompted me to take a look at the FDA warnings for TNF-alpha blockers. Apparently, the FDA started requiring cancer warnings on TNF blockers back in August of 2009 -- here's the FDA press release. I think dozens of cancer cases in children taking TNF-blockers prompted the FDA to add the box warning.

I definitely see the value of these drugs in the short-term to help get the inflammation under control, but long-term use doesn't seem like a solution. (Hence why I'm avoiding them!)

Why Pregnancy Pushes Autoimmune Diseases into Remission

A friend of a friend of mine has had Crohn's for many years. But when talking to her, she mentioned that during her pregnancy all her Crohn's symptoms completely subsided and she was in "remission". Why? This apparently is a common phenomenon for pregnant women with autoimmune diseases -- during pregnancy their diseases go into remission.

A new study from the University of Michigan may explain why. Apparently the expression of an enzyme called pyruvate kinase is reduced in immune cells in pregnant women. The reduction in this enzyme "dials-down" the immune system supporting the acceptance of the fetus.

An excerpt from the article:

In his search to explain the phenomenon, Dr. Petty knew to look for a metabolic pathway ormechanism with two characteristics. It had to "dial down" the intensity of the normal immune response, an action needed so that a pregnant woman does not reject the fetus, which has proteins from the father that are "foreign" to the mother. At the same time, such a mechanism must support cell growth needed by the developing fetus.

The activity of the enzyme pyruvate kinase–and its product, pyruvate–fills both roles: promoting cell growth while modifying the immune response. Because pyruvate kinase activity is depressed duringpregnancy, cell metabolism supports an increased production of lipids, carbohydrates, amino acids, and other substances that support cell growth.

This suggests an interesting alternative therapy or treatment option for the future (and I'm not suggesting that you just go get pregnant!). There may be a way to use this immune pathway in a drug therapy. It doesn't necessarily identify or address the root cause of IBD, but it could lead to another alternative therapy.

Gene Mutations Offer Clues to Autoimmune Disease

Saw a couple articles (BusinessWeek, Wired.com, ScienceNews) commenting on a story in Nature about a study that found that variations in a single gene could result in different types of autoimmune diseases, including Crohn's Disease and diabetes.

An excerpt:

The gene in question encodes an enzyme called sialic acid acetylesterase or SIAE, which regulates the activity of the immune system’s antibody-producing B cells. About 2 percent to 3 percent of people with autoimmune disorders have defects in the enzyme that allow B cells to run amok and make antibodies that attack the body, a team led by Shiv Pillai of Massachusetts General Hospital in Charlestown and Harvard Medical School reports online June 16 inNature.

“It’s a seminal paper because it is so applicable to a wide variety of autoimmune diseases, says Judy Cho, a Yale geneticist not associated with the study. The finding suggests that enhancing the enzyme’s activity could help treat disease in people with autoimmune disorders.

Definitely an interesting finding!

Resveratrol Improves Inflammatory Bowel Disease Symptoms

Saw an article about a new study that found that resveratrol, an antioxidant found in grapes, improved symptoms of inflammatory bowel disease (IBD).

Here's an excerpt from the article:

Resveratrol is a phytonutrient (phyto means “plant”) that is the subject of considerable research because of its anti-inflammatory, antioxidant, anti-tumor, and immune system boosting properties. Previous studies have suggested that resveratrol enhances brain function and builds resistance to stroke, helps withweight loss, inhibits prostate cancer cell growth, and protects against diabetes.

Resveratrol’s anti-inflammatory abilities are of special interest for possible treatment and prevention of inflammatory bowel disease, of which ulcerative colitis and Crohn’s disease are the two most common types. In the current study, which appears in theEuropean Journal of Pharmacology, researchers conducted a placebo-controlled study in which one group of mice were given 20 mg of resveratrol per kilogram of food and the other group received placebo. The study period lasted 30 days.

Grape juice is my primary dietary source of carbohydrates (because it is SCD compliant), so this is encouraging news. It also reinforces why the SCD diet may work.

Virus infection may trigger unusual immune cells to attack the brain and spinal cord in multiple sclerosis

I came across a really interesting article regarding a possible causative mechanism for multiple sclerosis (MS). As you most likely know, MS is an autoimmune disease (similar to IBD and Crohn's) where immune cells misguidedly attack the body's own cells. In the case of MS, the body is attacking the protective sheath around major nerves. In the case of IBD, the body is attacking your intestinal tissue.

The above mentioned article found that a viral infection could incite certain rare immune cells to be released in the body that attack both the virus and (in the case of MS) nerve cells. The rare immune cells do this because they have receptors for both the virus' proteins and proteins present in nerve tissue (myelin). I found this research interesting given the recent talk from Amy Proal that I blogged about regarding the viral and bacterial metagenome and the recent study (similar to the MS one) that found a possible link between errant T-cells and diabetes.

The study about MS suggests that there's not necessarily a single virus that causes the disease, but instead a combination of factors that generate the errant T-cells:

The authors explained that it's possible that multiple viruses could influence susceptibility to multiple sclerosis. The ability of any particular virus to contribute to the disease could depend on an individual's own repertoire of other predisposing genes, exposure to other predisposing environmental factors, and the random chance that T cells had been generated that recognize a myelin protein and a pathogen.

Receptors on T cells are randomly generated during their development. This observation helps explain why multiple sclerosis is partly a matter of chance. Some people with a genetic predisposition and environmental exposure develop the disease, while others with similar genetic predisposition and environmental exposure do not.

This suggests some really interesting (and challenging) directions for future research. Many current studies are focusing on finding a single bacteria or virus (e.g. MAP) that someone is infected with or a single genetic mutation (e.g. NOD2) that cause IBD. This is a potentially flawed approach, though. This study suggests that even after the infection is cleared, the errant T-cells that cause the autoimmune reaction may persist (i.e. there's no smoking gun). It certainly makes finding the root-cause difficult! But it suggests a different direction to take research.

Teaching Kids to Cope with IBD

Saw this article about a study conducted at the University of Georgia with teenage girls suffering from IBD. They found that teaching the young girls "coping" and "community" skills had a positive impact on their physical symptoms. They also found that mental distress decreased -- as they called it "catastrophic thoughts" (pretty scary sounding if you ask me).

Here's an excerpt:

"We saw significant improvements in these adolescents' physical symptoms and coping strategies following treatment," said Ronald Blount, professor of clinical psychology at UGA and an author of the study. "Parents, who were also involved in the study, reported reductions in catastrophic thoughts related to their daughters' pain and improved behavioral reactions related to their daughters' physical symptoms. We aimed to teach parents to become coaches for their daughters to help them better manage their symptoms."

Inflammatory bowel disease is a pretty life changing illness, though, and one quite difficult to talk about with others (particularly if you're a teenager), so I can certainly appreciate how important it is to teach young people these coping strategies. Stress certainly may play a contributing role in the disease, so stress reduction strategies may be helpful. The next step for the researchers is to expand the study to a larger population.

Meat Proteins Linked to Bowel Disease in Women

A new study from France revealed that eating lots of animal protein appears to increase the risk of inflammatory bowel disease (IBD) in women. The study was conducted on 67,000 women in France over a long time period to find risk factors for different diseases, including cancer and other common illnesses. There are no conclusions that are being drawn from the study, but it does suggest that diet does potentially play a role in the disease.

An excerpt:

Women who consumed the most protein were at more than triple the risk of being diagnosed with IBD, the researchers found; animal protein accounted for most of the risk. Risk was specifically associated with high intake of meat and fish, but not with dairy products or eggs.

While experts have long suspected that diet might play a role in inflammatory bowel disease, Carbonnel and his colleagues note, the only links identified previously were with eating a lot of fats and certain kinds of sugars. Those studies were more prone to error than forward-looking or prospective studies like the current investigation. There have also been several studies linking vitamin D deficiency to IBD.

Another excerpt regarding the potential link to IBD:

Meat could contribute to inflammatory bowel disease risk because digestion of animal protein produces many potentially toxic "end products," such as hydrogen sulfide and ammonia, the researchers note. Also, Carbonnel pointed out, a high-protein diet could alter the mix of bacteria that live in the colon.

The article doesn't comment on it, but I would argue that there is potentially another possible causation here. The reasons suggested are that the high intake of proteins is either generating toxic end-products or causing dysbiosis of the bacterial mix. If that were the case, though, this type of correlation would be present with other types of animal protein sources, including dairy and eggs. But there was not. (As an aside, I would also expect that other food types - e.g. starches, sugars, etc. - also produce these types of toxic end-products as well). I think another alternative cause could be the bacteria present in meat and fish stocks. Contamination from these food sources (e.g. MAP), could also be an explanation. Hopefully that's a third alternative they'll do additional research on. Either way, interesting study.

Probiotic in breastmilk reduces painful cramps

Thought this one was interesting. Apparently the bacteria Lactobacillus reuteri found in breastmilk decreases the force of muscle contractions associated with inflammatory bowel disease (IBD). It is passed on from mother to baby in breastfeeding. Interesting, but might be a tough one to add to your supplement list.

Here's an excerpt:

"It might not be possible for most of us to get breast milk from the tap," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but we can still benefit from some of the life-supporting substances it carries. This research shows that the relationship between humans and microbes can be beneficial for both. The Lactobacillus finds a new home, and we're no longer up tight."

Amy Proal on Viral and Bacterial Metagenome

Just watched a really interesting talk by Amy Proal about how the interaction and symbiosis (i.e. reinforcing relationship) between bacteria and viruses could lead to autoimmune disorders by interfering with Vitamin-D receptors (VDR's). I've embedded the video below, but here's a link to the post. It looks like she's working on some really interesting research.

The idea is that autoimmune disorders are caused by multiple bacteria and viruses working together to suppress the immune response. This causes a vicious cycle as it supports additional bacterial and viral infection. She suggests that traditional therapies like immunosuppression (which I have mentioned repeatedly seems counterintuitive) may actually prolong and worsen diseases in the long run. They have been working on alternative therapies that are meant to boost the innate immune response. Her blog seems pretty interesting as well, so worth a look as well: http://bacteriality.com/.