http://www.livescience.com/health/worm-therapy-stimulates-gut-mucus-101201.html

http://www.baltimoresun.com/health/la-heb-worm-healing-20101201,0,2645483.story

http://discussions.latimes.com/20/lanews/la-heb-worm-healing-20101201/10

From Scientific American: http://www.scientificamerican.com/article.cfm?id=helminthic-therapy-mucus

For the Good of the Gut: Can Parasitic Worms Treat Autoimmune Diseases?

Helminths could suppress immune disorders by promoting healthy mucus production in the intestine

By Ferris Jabr December 1, 2010

In 2007, parasite immunologist P’ng Loke sat down for lunch at a University of California, San Francisco, cafeteria with an inquisitive man who had called him earlier that week. Their chosen topic of conversation would deprive many people of an appetite, but the scientist and his guest shared an intellectual hunger for a stomach-churning subject: gut worms—specifically, tiny worm-like parasitic organisms called helminths that live nestled in the gastrointestinal tracts of their hosts.

Loke was fully prepared to answer the man’s questions about the parasites he knew so well, but what he did not realize was that his companion had more than just questions—he had worms burrowed in his intestinal walls, worms he had deliberately swallowed. Together, Loke and the worm-wrangler embarked on a research project, the results of which appear today in the December 2010 issue of Science Translational Medicine.

The 35-year-old man who had lunch with Loke was quite healthy in 2007. But only a few years earlier he was in the throes of an inflammatory bowel disease known as ulcerative colitis. An autoimmune disease, ulcerative colitis inflames the colon and leaves it rife with open sores; patients experience intense abdominal pain, vomiting, diarrhea, rectal bleeding and weight loss. While searching for treatments, the man discovered the work of Joel Weinstock, a gastroenterologist, parasitologist and immunologist at Tufts University who has pioneered research on helminthic therapy—treating autoimmune diseases by deliberately infesting patients with parasitic worms, such as whipworm and hookworm.

The results of Loke’s new case study—the most recent of only five studies that investigate helminthic therapy in people instead of animals—suggest that helminths may ease the symptoms of autoimmune diseases by increasing mucus production.

“It’s a unique study—there’s nothing like it before,” says Weinstock, who was not involved in the new research. “In this case they had a very unique patient—one who was self-infecting with helminths.” Clinical trials on helminthic therapy are particularly difficult to arrange because helminths are live pathogens and have not been officially approved as therapeutic agents by any governmental agency, although the U.S. Food and Drug Administration has granted pig whipworm (Trichuris suis) the status of Investigational New Drug. In contrast to human whipworm (Trichuris trichiura), the porcine variety cannot survive inside the human gut for very long.

“The researchers noticed a specific pattern of behavior, cycling between remission and active disease depending on when the patient infected himself with helminths,” Weinstock adds. “This is not a double-blind study, but the pattern is highly suggestive that the worms helped this patient. The major point of this paper is the potential mechanism—mucus production—which has not been looked at properly before.”

The Might of Mucus

In the new study, Loke—who is now with New York University—analyzed the man’s medical records prior to 2007 and personally tracked the man’s health from 2007 onwards. In 2004 the man swallowed a vial of salty liquid brimming with 500 human whipworm eggs, which he obtained from a parasitologist in Thailand. Three months later, he slurped down another 1,000 eggs. The larvae hatched and matured within his gastrointestinal tract, burying their heads in the intestinal wall. By mid-2005, he was virtually symptom free and required no medical treatment for his colitis, except occasional anti-inflammatory drugs to suppress flare-ups. The nearly complete dismissal of colitis symptoms is especially striking because human whipworm infection can itself cause digestive problems, including diarrhea, abdominal pain, nausea, vomiting and, in extreme cases, rectal prolapse. Severe infections can also cause anemia and stunt the growth of children.

In 2008, the number of whipworm eggs in the man’s stool began to dwindle, dropping from more than 15,000 per gram to fewer than 7,000 per gram. As the eggs disappeared, the symptoms of colitis returned. So the man infected himself with another 2,000 whipworm eggs and, a few months later, his symptoms practically vanished once again. Repeated colonoscopies revealed that wherever worms colonized his colon, the symptoms of colitis were significantly reduced or nonexistent.

During the 2008 relapse, the researchers found that immune cells in tissues with active colitis produced large quantities of an inflammatory signaling molecule named interluekin-17 (IL-17), but very little IL-22, the latter of which has been linked to wound healing and mucus production. When worms recolonized the colon, however, immune cells began manufacturing much more IL-22. Blood profiling and genetic analysis further revealed that tissues in which helminths thrived increased carbohydrate metabolism—a prerequisite for mucus production.

“Ulcerative colitis is often associated with decreased mucus production and the worms seem to somehow restore mucus production, possibly by inducing a population of immune cells that make IL-22,” Loke says. “It’s possible the mucus serves as a defensive barrier between bacteria and the gut that prevents bacteria from causing inflammation and crossing over into other tissues.” Autoimmune diseases generally occur when the immune system overreacts to benign—and even beneficial—organisms living within the body. In the case of colitis, researchers suspect the reaction is directed toward the bacteria in the gut. Loke thinks that the human body may boost mucus production when it detects helminths as a defense against the parasites; for a patient with ulcerative colitis, the extra mucus may also help calm an excessively aggressive immune system.

“We saw an association with remission and immune cells that make IL-22, but we don’t know for sure if these immune cells are actually induced by worms,” Loke says. “You can’t tell with a sample size of one,” which is especially susceptible to the placebo effect. Still, Loke adds, “the results seems quite compelling, especially when you consider the background—all the animal studies and clinical trials that show worms can suppress colitis and other autoimmune disorders.”

Mounting Evidence

In fact, in numerous animal studies, helminth infestation has protected rodents against colitis, asthma, rheumatoid arthritis, food allergies and type 1 diabetes.

Researchers have conducted few human studies, but most have shown promise. In a clinical trial published in 2005 in the journal Gut, Weinstock asked 29 participants with Crohn’s disease (another autoimmune inflammatory bowel condition) to ingest 2,500 pig whipworm eggs every three weeks for six months. Twenty-three patients (79.3 percent) improved significantly, and 21 (72.4 percent) experienced remission. Both the researchers and participants, however, knew exactly what treatment they were receiving, which makes excluding a placebo effect impossible.

In a controlled clinical trial published in 2005 in Gastroenterology, Weinstock and his colleagues gave 52 participants with colitis 2,500 pig whipworm eggs or a placebo every two weeks for three months. Thirteen of the 29 patients (44.8 percent) who received whipworm eggs improved, compared with only four of the 23 participants (17.4 percent) who received the placebo.

Weinstock and his collaborators point to these trials as experimental evidence that fits a global pattern: immune disorders are much rarer in less developed countries where helminthic infestation is widespread than in industrialized countries where much smaller populations host helminths. The “old friends hypothesis” proposes that the human immune system cannot learn to regulate itself without exposure to common pathogens like helminths that have coevolved with people and that modern hygienic practices deprive people of this necessary exposure, possibly explaining the relatively higher and more recent prevalence of immune diseases in industrialized countries like the U.S.

Loke plans to continue researching helminthic therapy in people and in monkeys. “We are talking about doing a small trial of, say, 10 people and basically doing colonoscopies on them before and after giving them pig whipworm,” he says. Loke also mentions that colitis plagues many juvenile monkeys in primate research centers and that he has received a pilot grant to treat diseased monkeys with human whipworm, an as-yet-unpublished experiment that is already returning promising results.

“When I first sat down to lunch with the guy who called me and he started telling me his story, I was really quite skeptical,” Loke recalls. “But now I am completely changing my mind about helminthic therapy.”

There’s a new film about to be released on using parasites as therapy by Sharon Shattuck called “Parasites: A User’s Guide”. Click on helminthic therapy and scroll down for a full list of research papers on using worms for various autoimmune diseases.  It looks like it will be entertaining, and she’s hoping for help with locations to screen her film, if you’ve got connections to your local movie theaters.  You can contact her through her website.

“The hope is that the work could aid the development of new treatments which work in the same way as gut parasites, by dampening down or rebalancing the immune system so that the body does not respond to allergens and trigger asthma attacks.”

“Here, the view is presented that assessment of the immunophysiological response to helminths could identify that infection with specific parasites would be therapeutically useful (although many helminths could not fulfil this role) and lead to precise knowledge of the immune events following infection, to identify ways to intervene in disease processes (in the absence of infection per se) that can be used to treat, and eventually cure, inflammatory and autoimmune disease.”

Dr. Joel Weinstock, one of the leaders in helminth therapy, criticizes operations like AIT for going ahead and giving out helminths before the research comes in:

“It is a legitimate field, but it’s been bootlegged,” said Dr. Joel Weinstock, a professor of medicine at Tufts University who’s studied parasitic treatment and is working to test the therapy. “The question is, what are you actually buying [from these companies]?”

(A face only a mother could love.)

“Parasitic gut worms, such as hookworm, might aid the development of new treatments for asthma and other allergies, a study in Vietnam suggests.

Infection with hookworm and other parasitic worms is endemic in Vietnam, but rates of asthma and other allergies are low.

British and Vietnamese scientists gave local children treatment to clear their body of worms.

They found this led to an increase in dust mite allergy among the children.”

This news report goes into greater detail:

“Dr Flohr has examined the links between worms and allergic diseases in Vietnamese children and found that those with the highest level of hookworm infestation were the least likely to have an allergic response to house dust mites.

These findings support the hypothesis that gastrointestinal infection with either hookworms or other micro-organisms protects against allergy and add further weight to the so-called ‘hygiene hypothesis’.”

Interesting that the highest level of hookworm infection had the greatest benefit. Clearly, dose matters.

I think I need more worms.

http://blogs.wnyc.org/radiolab/2009/09/07/parasites/

First, they start with Carl Zimmer, a parasitologist who talks about amazing interactions between parasites and hosts.  Then they discuss the hookworm eradication project, where it was found that the South was suffering from anemia, not laziness, and outhouses changed the course of history.  Then, an interview with Jasper Lawrence and his forays into Africa and how he started AIT (why do they never talk about how he got Necator Americanus?) And finally, a pice about toxoplasma gondii, a parasite that comes from cat feces that might influence  human behavior.  We are not all that we think we are.  We are being controlled by our bacteria and parasites as we speak.  Mhwah-ha-ha!

http://cbs5.com/health/hookworm.treatment.therapy.2.1015341.html

You can also view the video in their video library:

http://cbs5.com/video/?cid=119 Click on May 20th’s “Some Turn to Hookworms to Treat Ailments.”

And the Crohn’s one on hookworms:

http://cbs5.com/health/hookworm.treatment.therapy.2.1016319.html

You can also view it with a larger screen in the video library:

http://cbs5.com/video/?cid=119 Click on May 21st’s “Patients on Hookworm Therapy Swear by Treatment”

The opening is unfortunate. When we need to promote the idea of the hygiene hypothesis, and the fact that we are a walking microbiomes, the choice to sensationalize “eating worms” is disappointing. I didn’t eat 6 dirty earthworms, for God’s sakes. Hopefully the general public will be interested and not just further disgusted. Enjoy!

Professor Anne Cooke: “It will allow you to identify pathways of disease and allow you to modify them with small molecules, not the whole worm.”

“Before I would even consider treating a child with type 1 diabetes I would have to be sure it was safe and understand the mechanisms underlying it.

“We are talking about using fractions not the whole parasite.”

What they don’t recognize is that in the meantime, there are desperate patients like me, absolutely willing to try worms to alleviate our diseases. Especially as the choices we have are so dangerous – a small colony of hookworms or whipworms that only cause transient side effects (and this is written by the side effect queen), or Tysrabi, with a 1 in 1000 chance of progressive multifocal leukoencephalopathy? If I were a parent of a child with type 1 Diabetes, or Crohn’s, I would absolutely jump at the chance of trying a light hookworm infection rather than the alternative. How many decades until Professor Cooke and others figure out those fractions of parasites? I would lose another piece of my intestines.

We want worms now.

“Studies (Weinstock) has conducted with Dr. David Elliott, a gastroenterologist and immunologist at the University of Iowa, indicate that intestinal worms, which have been all but eliminated in developed countries, are “likely to be the biggest player” in regulating the immune system to respond appropriately, Dr. Elliott said in an interview. He added that bacterial and viral infections seem to influence the immune system in the same way, but not as forcefully.

Most worms are harmless, especially in well-nourished people, Dr. Weinstock said.

“There are very few diseases that people get from worms,” he said. “Humans have adapted to the presence of most of them.”