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11-19-2010, 05:29 AM   #1
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The root cause and cure for IBD: Univ of Iowa's new theory and research

Worm Therapy: a New Treatment for IBD?
Worm therapy offers hope for patients suffering from painful and debilitating diseases such as Crohn's and ulcerative colitis (Inflammatory Bowel Disease)

7/1/2004
Saturday Evening Post
By Patrick Perry

Have efforts to cleanse and safeguard our environment and health inadvertently placed us at greater risk for certain diseases?

Some researchers believe so.

During the past 75 years, industrialized nations have increased hygiene and reduced exposure to various types of microorganisms. People left farms and migrated to urban areas, donned shoes, erected cement walkways, and structured the landscape to eliminate any environmental exposure to bacteria and microorganisms in the belief that all were harmful. Crohn's disease was first recognized in the Jewish populations of New York City in the 1930s but soon surfaced in other ethnic groups and countries around the world. Over time, scientists noted an increase in other disorders of the immune systems, including multiple sclerosis, allergies, and type 1 diabetes.
Looking for an explanation for the increase in IBD and other disorders, a team of researchers at the University of Iowa began to focus on what we may have left behind when we moved from rural communities to urban areas. By eliminating microorganisms that inhabited the human gut, did the human body become more vulnerable to immune reactions?

The team developed the IBD hygiene hypothesis, proposing that raising children in extremely hygienic environments may have had a negative impact on immune development, predisposing children to immunologic diseases like IBD. They also postulated that modern hygienic practices have led to significant reduction in exposure to certain helpful parasites called helminths, or worms, that help regulate host immune systems and prevent excessive inflammatory responses, which could underlie a mechanism of protection. Indeed, helminths boast broad immunoregulatory properties that evolved over the centuries into a successful host-parasite interaction.

One's initial impulse when thinking about "worms" is to get rid of them, but they perform a unique function in the human immune system. They help dampen the inflammatory immune response, specifically the type 1 T helper cell response, which reacts to bacteria or viruses that invade the bloodstream. The research group believes that eliminating worms may also eradicate one of the few environmental factors that help prevent IBD.

To test their hypothesis, the team decided to try worm therapy. Several years ago, the team treated severely ill IBD patients with the eggs of worms, specifically Trichuris suis (or pig whipworm), which is similar to the human whipworm. During the six-month study, five of the six patients went into remission that lasted between two to five months. On follow-up, patients were given the agent once every three weeks, and the team found that with this dosing schedule, they could maintain remission. People who were chronically ill for years went into complete remission--no diarrhea, no abdominal pain, no joint problems.

The University of Iowa team began conducting further double-blind studies of helminthic (worm) therapy for patients with Crohn's disease and ulcerative colitis with further success. To learn more about current research and ongoing trials of this hopeful treatment for IBD, the Post spoke with gastroenterologist Dr. Joel Weinstock, professor of medicine and director of the division of gastroenterology and Center for Digestive Diseases at the University of Iowa, who is spearheading the therapy.

Post: Could you tell us about your ongoing study of helminth (worm) therapy for patients with inflammatory bowel disease?
Weinstock: When talking about inflammatory bowel disease (IBD), I am referring to ulcerative colitis and Crohn's disease. Both are inflammatory conditions of the intestine that typically begin when people are in their teens or 20s.

People with IBD experience recurring, chronic symptoms that include diarrhea, abdominal pain and blood loss through the gastrointestinal (GI) tract, among other problems that result from inflammation of the intestinal tract, and these symptoms can persist for years.

IBD seems to be on the increase. While once very rare to see a patient with Crohn's disease or ulcerative colitis, today it is extremely common.

Although the diseases have probably been with us for some time, they were not recognized until the mid-1930s. Other diseases are following the same pattern. For instance, multiple sclerosis seems to be of modern derivation.

Post: Why are these diseases on the increase?
Weinstock: We think that immunological diseases are on the rise due to lifestyle.

In the late 1990s, my colleagues and I considered possible causes of Crohn's disease. While we sifted through the data, one thing that impressed us was that these are diseases with a geographical preference and are increasing in frequency.

For instance, IBD is known to have a North-South gradient. Crohn's disease is common in the North and rare in the South of the United States, and the same is true in Europe. Worms fare better in warmer climates, so people who live in the South are more apt to have worms than people in the North. While prominent 50 years ago, these gradients are disappearing. IBD, for example, is increasing in frequency in Japan, South Korea, and wherever the quality of life and living standards are improving.

Today, IBD is estimated to affect about one in every 250 people in some regions of the United States. At one time, the disease affected about one in 5,000 Americans, so the incidence is increasing. While we are now living better, longer, and cleaner, we are getting a new category of disease, one that is not the same disease of old.

Post: What are helminths?
Weinstock: We have been studying organisms known as helminths, worm-like organisms that live In the GI tract. When you go to the bathroom, you excrete waste that is about 50 percent live bacteria. You are teeming with life. And this life within is important for helping you digest food, toning the immune system, and producing vitamins. You need gut "flora," or bacteria. If you lose intestinal flora, you won't be healthy. As a species, we evolved with intestinal flora. Humans and other animals have coexisted with helminths since the dawn of time. When you think about it, you are talking about millions of years of coevolution. These organisms need us to survive; otherwise, they become extinct.

In the real world, almost everyone had worms. They are very common in children, who get worms when exposed to contaminated soil and by swallowing the eggs. At least one third of the people around the world today have worms in their GI tract.

Post: When did this begin to change?
Weinstock: In the 1930s, we started deworming everyone. We did it directly by giving people antiworming agents and indirectly through sanitation. Kids used to run around barefoot. Some forms of helminths you pick up through skin. If you drink out of a well or stream, you can pick them up. Now we wear shoes and have water filtration systems, so our water is very clean. The same is true with food. Today, food is much cleaner than it was 70 years ago, so children aren't getting these worms.

Post: As a result of deworming our environment, are we now at greater risk for certain diseases?
Weinstock: In the U.S. and industrialized countries, worms are no longer part of the GI tract. There is a direct inverse relationship between worms and immunological diseases. People who have worms don't tend to get immunological diseases, while people without worms do. This coincidental association led us to hypothesize that perhaps worms are a protective factor and that deworming was not a good Idea.

Worms are also protective because they stimulate aspects of our system that help to dampen hyperreactive immune systems. Minus worms, Immune systems tend to react much faster and may lead the human body to overproduce powerful substances that lead to excessive inflammation of the intestinal tract. Deworming results in a hyperactive immune system. This is a known fact.

This process of deworming may be one of the factors leading to the expansion and emergence of a variety of immunological diseases, such as childhood asthma, that are very common in the United States and England. In many less developed countries, asthma is infrequent.

Another example is hay fever. In some countries, this disease is rare--zero. But perhaps 20 to 25 percent of the American population has to live in air conditioning and can't go outside at certain times of the year. That Is not the normal state of affairs. While we learn to live with it, It isn't right.

To make a long story short, we have shown what intestinal worms can do to dampen the Immune system, and how they work. In clinical studies, we actually gave worms to people with IBD, with very good results.

Post: Do most people in the U.S. still carry worms, and how would one know?
Weinstock: Most people don't carry them; you can tell if people have helminths. But not everybody without helminths will get an immunological disease. Luck, genetics, and certain other triggers must be present for the disease to emerge. But if you have helminths, we believe that you will be less likely to get IBD because you have protective factors. A virus, for example, is less likely to trigger the disease in someone with helminths.
ARTICLE CONTINUED.......
11-19-2010, 05:29 AM   #2
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Post: How do you introduce worms into patients?
Weinstock: Every two weeks, patients consume a few ounces of a liquid to which are added microscopic eggs, but you cannot see anything in the drink.

We use a worm that is extremely safe and stays in people's systems for a very short time. It is almost invisible, so you can't tell you have them.

There have been no recognizable side effects, and this worm cannot be transmitted to anyone around you.

Post: What do the helminths do inside the intestinal tract?
Weinstock: They hatch out of the eggs, grow into small organisms, then the immune system of the host reacts to these organisms and eventually gets rid of them. The interaction between worms and the human immune system triggers the regulatory pathways that down-modulate the inflammation that dampens the inflammatory response. They are turned off.

Post: How long have you sustained a remission in patients?
Weinstock: In some patients, we have sustained remission beyond four years. Remember, we are not talking about 100 percent of people with IBD. We are talking about a subset of patients; some don't respond; some respond, then relapse a year later; while other patients respond and stay responsive--they don't get sick again.

Post: Do responsive patients have both a genetic susceptibility and an absence of helminths?
Weinstock: Not necessarily. That would imply that helminths are essential. But disease could break out in people who have worms. You must think of two issues--prevention and treatment. Once a disease is established, it is hard to reverse--the proverbial horse is out of the barn. And getting the horse back in the barn becomes harder. Treatment may help.

Children exposed to worms and these organisms growing up may be much less prone to developing ulcerative colitis, Crohn's, multiple sclerosis, hay fever, allergies, and other diseases. But once the diseases develop, you have to convert an aberrant immune system into one that is more normal, which is more difficult to do.

Post: Are people in remission also still on anti-inflammatories or other IBD-type medications?
Weinstock: We always try to taper them off of other immunomedicines or get them down to a minimal dose. The most successful patients have been able to get off of more dangerous agents.

Post: How do people overcome any initial hesitation of swallowing worms?
Weinstock: Patients in the trial are not afraid. Given the choice of taking medications like the steroid prednisone and the immunosuppressant Imuran for years with all the unpleasant side effects, or swallowing some harmless eggs every two weeks with no side effects, which path would you take? The therapy is not as yet perfected. We are at the very beginning of what we hope will be a breakthrough.

Post: This new approach sounds very promising and hopeful for patients with IBD.
Weinstock: We now have important clinical data suggesting that the idea is correct. Nothing is absolute in science, however. This organism resides in pigs--about 20 percent of pig herds carry the worms. Farmers who raise pigs may be exposed to the organism. It is a well-recognized observation that people who are raised near big animals are less likely to get asthma or immunological diseases. Perhaps exposure to animal worms is one of the reasons.

Post: What has been the reaction of fellow gastroenterologists?
Weinstock: Originally, we had lovers and haters, as one would expect of any new theory. Right now, it is becoming much more widely accepted. In the next couple of years, you will hear a lot about it.

The real value of an agent could take years of testing. How many it will help, for how long, whether it might actually cure some people or become a supplement remains to be seen. Much work still needs to be done.

Using a treatment regimen of worms, doctors at the University of Iowa are helping patients with Crohn's disease and ulcerative colitis. Dr. Joel Weinstock and his team have found that patients who swallow a mixture of the helminth or parasitic worms suspended in Gatorade achieve relief and remission from IBD. Every few weeks, patients return to the clinic to repeat the treatment: if they do not, symptoms return.
11-26-2010, 12:20 AM   #3
freezulu
 
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This is a very informative website on the topic..........

helminthictherapy.com
11-28-2010, 09:54 PM   #4
Nica
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I remember something about worm therapy going on in the late 90ies early 00's.. I was so icked out by the thought of drinking worms.. LOL now I might just do it to make this thing go away!
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11-28-2010, 11:03 PM   #5
BLM
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I think that this is really fastenating. Amazing how through time weve tried to better ourselves in certain aspects, yet have been detramental in other ways. I think its an interesting theory, and it makes sense. I would be open to trying out the worm treatment, if it offered relief!
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11-29-2010, 12:37 AM   #6
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Nica, icked out doesn't begin to describe it. I'm seriously phobic about worms (I rode on an 80 foot high zip line yesterday, but I freak out at the sight of a worm). They'd have to knock me out for the duration of the treatment, lol.
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11-29-2010, 02:12 PM   #7
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Kelly,
LOL It would take A LOT to get me to drink something I knew had worms in it. That would just be my luck, they finally find a cure for crohns and I am too icked out to do it ROFL.
11-29-2010, 04:51 PM   #8
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I don't think someone could pay me to drink worms!
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11-29-2010, 05:01 PM   #9
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Plus I always look at how these articles were in 2004, 2007, etc and think "If this was really the answer.....wouldn't more people be doing it?" BTW I'm ICK on the worms too. :-)
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12-06-2010, 10:36 PM   #10
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Oh, no no no no no no. Anything, but worms.
12-07-2010, 01:28 AM   #11
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Looked into this option a few years ago but doc said it's only effective if your Crohn's is in the early stages ie only been diagnosed in past 3 yrs.
12-09-2010, 04:48 PM   #12
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^ that doesn't make sense to me. Crohn's causes ongoing damage. If you have surgery, it would mean as if your disease is "new" again, would it not?
12-10-2010, 12:15 AM   #13
freezulu
 
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Here's another current news article on the topic.........
cnn.com/2010/HEALTH/12/09/worms.health/index.html
12-10-2010, 03:20 AM   #14
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One word: Ew. Lol, the thought of swallowing egg worms is disgusting enough! But if it ends up working, it'll be a small sacrifice to pay!
12-10-2010, 05:45 AM   #15
freezulu
 
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Yes, I agree.. not a pleasant thought to injest tiny worms. But, if it can heal you and stop the horrible symptoms of bleeding and urgency then it's well worth it!!!
12-10-2010, 11:28 PM   #16
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I talked to my GI about my daughter as she was beginning the first of her flares- we were just piecing together her CD. He recommended that I let her go out in the back yard, play barefoot, and eat dirt. He is from another county and is adimant that westerners have an unhealthy obsession with antibacterial everything. He really believes that it is a contributing factor in IBD and other immunological diseases- rarely seen is less developed parts of the world.
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12-11-2010, 11:30 AM   #17
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OK, how do I sign up?
12-12-2010, 04:07 AM   #18
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Well I used to play outside barefoot. And then bite my toenails. I never ate dirt, but I do recall drinking rainwater from puddles. Oh, and I used to eat grass. If I cut myself or grazed my knee, I would just lick it clean. And I don't think I ever washed my hands (unless they were absolutely filthy!). So I don't think that my Crohn's at least was caused by over cleanliness!

As for drinking the worms, they're microscopic, so it's only as gross as drinking bacteria (ie probiotics).
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12-12-2010, 08:23 AM   #19
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I do have an issue with the theory. They have said that one of the kings from early England had Crohns. So eh. I used to eat fruit right from the garden all the time as a kid, so I am sure I got LOTS of dirt and whatnot.

I remember when this was a new study and mentioning it to my GI. He flat out said I am not going to recommend it to any of my patients. So I think I would need more testing before I went and drank a bunch of tiny worms.
12-12-2010, 03:08 PM   #20
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I think this could be a good therapy for one to consider trying if conventional meds fail.

Last edited by Guest9283; 12-12-2010 at 05:12 PM.
12-13-2010, 09:31 PM   #21
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I would think this may be out of date and probably not so new anymore. The study alone is 6 years old from the time it was published likely meaning they did the trials between 7-10 years ago. Would be interested to see if anyone has spent the money to retry this theory in another study since.
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12-15-2010, 07:31 PM   #22
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I'd like to ask my doc just to see his face, lol.

I had a very outdoorsy and germ-filled childhood. I've had cats and dogs my whole life, still do, and have cleaned up tons of poop, urine, and litter. Surely my intestinal worm situation is up to non-western standards, right?
12-22-2010, 06:31 PM   #23
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Any chance of somebody in Australia getting sent some of these parasites in a viable, orally taken form? I am keen to try! I was bought up in a tiny shack in the rainforest, and my parents have assured me that it was anything but overly clean.....but they have told me that they used a chemical to fix holes in the watertank that somehow got into the water supply.
12-22-2010, 09:25 PM   #24
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It's not necessarily how "outdoorsy" you are, it's sanitation in general. We don't usually have parasites in our drinking water, which is one reason they think third world countries have virtually non-existent rates of this disease. That doesn't mean it wouldn't ever happen (early king of England for example), but that it could be one of the major reasons why. The hygiene hypothesis has been around since 1985, and growing more and more evidence that supports it (they also think our sanitation has caused other diseases not typically seen in third world countries, such as allergies and asthma).

In the case of Crohn's disease, the theory is such that parasites are known to have mechanisms to turn off your immune system. If a parasite is in your gut protecting itself, it will have to turn your immune system off in that area, which will in turn keep your immune system from attacking its own cells. I think it's actually fairly sound logic. Wish a drug company could/would copyright it so it would be worthwhile for them to do a real study on it. *le sigh*

If you are creeped out by eating "worms" you might want to pull all you eyelashes out. There are mites that live on them that are about as worm like as the worms you're thinking of. http://en.wikipedia.org/wiki/Demodex Among other parasites humans live with.
12-22-2010, 10:40 PM   #25
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EWWW! OMG I'm so creeped out! I had a friend get a parasite worm in Central America and this just freaks me out!
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12-23-2010, 04:31 AM   #26
Andy108
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Thanks Diesanduhr, very informative.....my parents have told me that we lived in "filthy" conditions, not just outdoorsy....actually their house is still rarely cleaned properly, they say they "are just not interested in housework" hahaha.

It is possible that I was kept antiseptically clean as a baby though, as my Mum explains they were quite overboard with me as I was the first child.
12-23-2010, 10:13 AM   #27
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Hi all,
Company Dr Falk (w_w_w.drfalkpharma.de), producer of Budenofalk, saloflk and etc. started massive clinical trials using TSO (Trichuris suis ova) for CD in more than 13 different clinics in Germany!! Phase II.
Information in German: (w_w_w.drfalkpharma.de/nc/start/falk-aktuell-fachkreise/article/ursofalkR-kann-nicht-substituiert-werden/?tx_ttnews[backPid]=4902&cHash=d38765cf4b]

This is the first massive clinical trials for CD!!
12-23-2010, 10:18 AM   #28
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CNN) -- One day in 2004, a 29-year-old man with a terrible stomach problem stepped off a plane from the United States in Thailand. He wasn't there for the sights, or the food, or the beaches. He had traveled thousands of miles for worms -- parasitic worms whose eggs he intended to swallow by the thousands.

His doctor back home had told him his idea was crazy, that infesting himself with parasitic worms wouldn't do anything to help his ulcerative colitis, and in fact could make him very sick. The gastroenterologist had told the man if he pursued this course of treatment, he would refuse to be his doctor anymore.

"You'll be on your own," the man remembers the doctor telling him.

Indeed, he was on his own, standing in the office of a Thai doctor, asking her to pick the worm eggs out of an 11-year-old girl's stool.

Ten to 15 bloody bowel movements a day

This month, the man's experience treating himself with parasitic worms was published in a medical journal. Depending on who's telling the story, his journey is one of a brilliant, empowered patient who found an amazingly effective treatment for himself and possibly others who suffer the same debilitating disease -- or the dangerous tale of an irresponsible medical rebel who could have killed himself and, by telling his story, might be inspiring others to do the same thing. As with any experimental treatment, you should not try this at home.

The man -- who wants to protect his privacy, and be referred to only as "the patient" -- was 28 when he started having bloody bowel movements. Soon, he was having 10 to 15 bloody bowel movements a day.

"I was constantly running to the bathroom," he remembers.

Diagnosed with ulcerative colitis, nothing helped except high doses of steroids, which because of severe side effects, he could take only for limited periods of time. Soon, the patient became so sick he had to quit his job.
How to get the best medical care
Elizabeth Cohen on her new book

His gastroenterologist wanted to admit him to the hospital for an intravenous round of cyclosporine, a potentially helpful yet dangerous medicine that depresses the body's immune system and can increase the risk for getting cancer later in life.

If the cyclosporine didn't work -- and there was a 50 percent chance it wouldn't -- the doctor said his last hope was to remove his colon entirely, an extreme measure that would cause him to have to have a colostomy bag attached to him for the rest of his life to collect his stool.

"I was really at the end of the road," he says.

Meanwhile, the patient had gone on the internet and found an article in a medical journal by Dr. Joel Weinstock, chief of gastroenterology at Tufts University Medical School, which showed some ulcerative colitis patients found relief after ingesting the trichuris suis worm, a parasite that lives in the intestines of pigs.

The patient contacted Weinstock to ask him to treat him with worms, but Weinstock said no, since it wasn't approved for general use by the Food and Drug Administration and could only be done experimentally.

Other doctors also told him no.

"One very famous parasitologist in New York told me he had patients who were immigrants, and he could get the eggs from their stool," he says. "But he told me for legal reasons he couldn't do it. I understood completely. What if something went wrong and I died? He'd be blamed."

The patient became more and more convinced worms could help him. Behind Weinstock's study was this observation: Inflammatory bowel diseases such as ulcerative colitis affect nearly one in 250 people in the United States, but are extremely rare in underdeveloped parts of the world, such as sub-Saharan Africa.

Some experts believe parasitic worms might be part of the reason. When underdeveloped areas become developed, parasitic worms, also called helminths, become less common, and diseases such as ulcerative colitis become more common.

"We're not exposed now to helminths in places like the United States, and that probably has an impact," Weinstock says. "We've tried to separate ourselves from our natural environment with our sterile water and our sterile food, and that's saved lives, but there are negative consequences."

A 'terrible choice'

"I was facing a terrible choice," the patient remembers, between going with the doctor's treatment idea, which he really didn't want to do, and looking outside the United States for worm eggs to ingest.

He contacted researchers in various developing countries to ask if they could help him get his hands on some eggs. The researcher in Thailand was particularly helpful, and he got on a plane to visit with her.

After he arrived, the doctor in Thailand extracted roundworm eggs from the stool of an 11-year-old infected girl. She gave the trichuris trichiura eggs to the patient, but he now faced another hurdle. The eggs needed to be cleaned in case the girl had hepatitis or some other infectious disease, and the eggs needed to mature for them to be helpful. It was up to him to clean the eggs and grow them in a process called "embryonation."

"There wasn't much guidance on how to do it, since most people are trying to destroy these worms, not grow them," he says.

But he managed to do it and ingested first a dose of 500 eggs and then another of 1,000. The worms could live in his intestinal tract for many years.

Three months later he had fewer bloody bowel movements, and soon, none at all. His bowel movements were normal. He felt fine.

From time to time, when his ulcerative colitis would flare up again, he'd extract eggs from his own stool, and clean, embryonate and ingest them. Again, his symptoms would go away.

A reluctant researcher

By 2007, having made so much progress, the patient wanted to document his journey scientifically, and he contacted various researchers to help him, including P'ng Loke, who was then a postdoctoral fellow in immunology at the University of California-San Francisco.

"He e-mailed me, and I ignored it," Loke remembers. "I was very skeptical at first, but he convinced me to have lunch with him."

At their meeting, the patient laid out his story in more detail, and Loke became fascinated.

"It's an amazing story, and he's quite possibly one of the smartest people I know," he says.

By the end of their meeting, they'd started to hatch a plan: Loke and his team would do colonoscopies to track the patient's ulcerative colitis and look for the presence of worms in his colon.

The researcher, now an assistant professor of medical parasitology at New York University Langone Medical Center, and his team did a colonoscopy on the patient, which revealed an abundance of worms and no signs of ulcerative colitis.

When the patient suffered a flare-up of his disease in 2008, a colonoscopy showed fewer worms and typical signs of ulcerative colitis.

When he ingested more eggs, a third colonoscopy showed the colitis was once again in remission.

The study was published in this month's Science Translational Medicine.

Why worms might work

To figure out why the worms seemed to be having this beneficial effect, Loke and his colleagues took a close look at the patient's immune system after he ingested the worm eggs. After ingestion, he had an abundance of cells that produce a protein called interleukin-22, which is important in healing the mucosal lining of the intestines.

"Our main conclusion is that the worms were able to restore mucus production in his gut," Loke says, adding that the mucus lining protects the intestines from harmful bacteria.

But others are not so convinced.

"The impact of mucus alone is not a scientific explanation for the possible improvement attributed to the worms," says Dr. Stephen Hanauer, a member of the board of trustees of the American College of Gastroenterology.

Charges of irresponsibility

Hanauer, chief of gastroenterology, hepatology and nutrition at the University of Chicago, warned against making too many conclusions from one man's positive experience with worms.

"We don't make medical recommendations based on a single case report," he says.

He says New York University was "irresponsible" for putting out a press release about the study, and criticized media outlets such as CNN for reporting on it.

"It's ridiculous and incredibly inappropriate," he says. "You're driving people to go on the internet and buy these worms, and these are potentially pathogenic organisms. These eggs can invade the systems of people who are immune suppressed and cause infections."

Loke says he and his team pointed out in the press release that the worms might hurt some people rather than help them.

"I agree no one should be trying to change their treatment" based on the paper's findings, Loke says.

The patient says he is also concerned others might try to copy him with potentially disastrous results, and so declined to explain exactly how he cleaned and embryonated the eggs.

He says he knows he took a risk by ingesting the eggs from a young girl in Thailand, but for him it was a better option than treatment with drugs that have potentially dangerous side effects, or the removal of his colon.

"Sometimes you really do have to take matters into your own hands," he says.
h_t_t_p://edition.cnn.com/2010/HEALTH/12/09/worms.health/
12-23-2010, 10:22 AM   #29
Igor_Passau
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ES-62 is a protein that is actively secreted by filarial nematodes during parasitism of the vertebrate host. The molecule is able to directly interact with a number of cells of the immune system including B-lymphocytes, dendritic cells, macrophages and mast cells. Interaction appears to be dependent on complexing with TLR4 and results in modulation of the activity of a number of signal transduction molecules including MAP kinases, PI-3 kinase and NF-kappaB. Immunomodulatory activity of ES-62 appears to be largely due to the presence of phosphorylcholine (PC) moieties covalently attached to N-type glycans. The net effect of ES-62's interaction with the immune system is the generation of an anti-inflammatory immunological phenotype. As a consequence of this, ES-62 demonstrates striking drug-like activity in models of disease associated with aberrant inflammation, in particular those associated with autoimmunity and allergy.

w_w_w.ncbi.nlm.nih.gov/pubmed/20054977

2009
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
12-23-2010, 10:22 AM   #30
Igor_Passau
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Helminths may protect humans against allergic and autoimmune diseases and, indeed, defined helminth-derived products have recently been shown to prevent the development of such inflammatory diseases in mouse models. Here, we propose that helminth-derived products not only have therapeutic potential but can also be used as unique tools for defining key molecular events in the induction of an anti-inflammatory response and, therefore, for defining new therapeutic targets.

2010

w_w_w.ncbi.nlm.nih.gov/pubmed/20224568

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
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