WALL STREET JOURNAL
HEALTH
JUNE 28, 2011, 3:46 P.M. ET
Parasitic Worms May Offer Hope on MS
By STEN STOVALL
For people suffering from debilitating autoimmune disorders such as multiple sclerosis, there is growing evidence that help may be at hand from an unusual source: parasitic worms.
In a U.S. study, early safety tests suggested the eggs of pig whipworms have anti-inflammatory properties, reducing the size of brain lesions in MS patients. A similar trial is under way in Denmark. And in Britain, academics at the University of Nottingham are studying the potential health benefits of hookworms, another type of parasitic worm.
If these trials prove successful, treatment with parasitic wormsknown as helminthic therapycould provide a simple, cheap, natural and controllable treatment for the debilitating condition, which affects 2.5 million people world-wide.
Multiple sclerosis is an inflammatory disease of the brain and spinal cord, in which an overactive immune system attacks the nerve fibers responsible for sending signals to the rest of the body. Its symptoms include impaired vision, muscle weakness and spasm, fatigue, memory loss and depression.
Medication can slow the disease's progression, but many of the drugs on the market have unpleasant side effectsincluding hair loss, muscle aches, fever and nausea, sleeplessness and flu-like symptomsor more dangerous risks including organ damage and brain infection.
The market in MS drugs was worth about $12.6 billion in 2010, according to research firm Espicom. Top-selling Copaxone, an injectable treatment made by Teva Pharmaceutical Industries Ltd., generated $3.3 billion in sales that year.
Interest in helminthic therapy surged in 2007 with the publication of a study in Argentina by physicians Jorge Correale and Mauricio Farez. It showed that the progression of multiple sclerosis was much slower in patients who carried parasitic worms in their intestines than in those who didn't.
A study recently published in the Multiple Sclerosis Journal suggested the pig parasite Trichuris suis ova whipworm, which lives in the host's intestine, is effective in treating MS symptoms.
"The results are quite promising," says John Fleming, a professor of neurology at the University of Wisconsin School of Medicine and Public Health, who led the study.
Five patients took part in the Phase 1 trial, called Helminth-Induced Immunomodulation Therapy, or HINT. All were newly diagnosed with relapsing-remitting MS, a form of the disease in which new symptoms can appear and old ones resurface or worsen.
Whipworm eggs were taken from disease-free pigs and grown in Denmark in a clean environment by a German biotech company, OvaMed GmbH. Every two weeks over the course of three months, the patients in the study drank 2,500 of the eggs mixed into a sports drink. The eggs hatched in the patient's intestines and were killed by the immune system after about a week.
Patients who took part said the liquid was salty but didn't taste or smell unpleasant.
"It was like drinking a shot of salty wateryou didn't notice the worms. It wasn't like there was anything chunky in it," explains Jim, 40, the first patient recruited for Dr. Fleming's safety study, who asked not to have his surname published.
"I signed up shortly after being diagnosed and didn't have a problem with it because I was pretty scared and, for me, ingesting worm eggs is just not a big deal."
During the HINT study, patients underwent MRI scans, which tracked the number of new brain lesions that developed before, during and after they ingested the worm eggs.
"What makes us optimistic is that brain lesions in four out of the five patients decreased over the course of the study and then reboundedor roseagain after it finished," says Dr. Fleming. While the pattern shown by the MRIs is encouraging, he adds, larger and longer studies will be needed before any definite conclusions are possible.
Researchers say the Wisconsin study's findings could mean that the immune system's over-response to the brain tissue was lessened by anti-inflammatory effects from the worms, and this could offer an alternative approach to treating MS.
Dr. Fleming's HINT1 trial, which was funded by the U.S. National Multiple Sclerosis Society, will be followed by a bigger HINT2 study.
"We're now going forward and are midway recruiting 18 new MS patients for a Phase 2 trial that will last 10 months, with final results probably announced in around 18 months or so," he says.
In Britain, a similar study is being planned using parasitic hookworms. Funded by the U.K.'s Multiple Sclerosis Society and conducted by the University of Nottingham, the Phase 2 clinical trial, called Worms for Immune Regulation in MS, or WIRMS, will involve 70 patients.
"The worms will be administered to patients through applied arm patches, burrowing from there through the skin and giving a live infection," explains Doug Brown, head of biomedical research at the U.K. Multiple Sclerosis Society. After nine months, the worms are flushed out with a de-worming tablet called mebendazole. Patient recruitment starts this summer and the study's findings should be published in around three years' time, says Professor David Pritchard, the co-lead in the WIRMS study.
Prof. Pritchard, an immunologist-biologist, says that while the Wisconsin study uses worms found in pigs, "we're using a human parasite that lives only in people, and we believe it has advantages. We have worked with this parasite for decades, so we understand its biology."
As part of his investigation, Prof. Pritchard allowed himself to be infested with hookworms. He admits he was nervous at the time.
"Too many [worms] could cause tissue damage. And, once they are on the skin, there is no going back, until the worms reach the gut, from where they can be eliminated with worming medicine," he explains. He says he felt intense itching within seconds of the worms hitting his skin. "Thereafter," he says, "there was a feeling of intestinal discomfort as the worms grazed on the intestinal tissues."
Prospective patients need not be put off by Prof. Pritchard's experience, though. Whereas he was infected with 50 worms, patients in the study will receive lower doses. Following on from safety studies, 10-25 worms were chosen, because of the relatively asymptomatic nature of infection with lower doses.
Longer-term recipients of 10 worms report an easing of mild gut symptoms as host and parasite seemingly reach a form of biological agreement. "It is at this point that we hypothesize that immune regulation may be taking place, as the worms suppress the immune system to ensure their survival," he says.
Prof. Pritchard says the trial will assess whether the worms' presence can prompt the activity of a subset of the immune system's white blood cells, regulatory lymphocytes, which tone down the inflammation that causes allergies and autoimmune diseases.
The theory behind the HINT and WIRMS studies and others like them is known as "the hygiene hypothesis." This argues that developed countries such as the U.S., Europe and Japan have higher incidences of allergies and autoimmune diseases because the population has little or no exposure to parasites or infections.
In developing countries, where people are exposed to low-level infections or infestations, the rates of such diseases are much lower.
"If we get a sterile environment, like we have in Western countries for the last century by and large, an unintended consequence may be that the immune system develops in abnormal ways. That it may overreact against the patient's own tissues," explains Dr. Fleming, who led the Wisconsin study.
Alasdair Coles, a neurologist and researcher specializing in MS at the University of Cambridge, is aware of the planned WIRMS trials but isn't involved in them.
He says helminthic therapy is "potentially useful." It is "relatively cheap, relatively easy, relatively safe and all that matters is that we find out how efficacious it is."
But, he warns, the potential benefits may be overstated. "My prediction will be that this will be a safe but only partially effective therapy," he says. "The data that we have so far, which is very little, would suggest that efficacy is rather low; real, but rather low."
Shana Pezaro, a 32-year-old living on the south coast of England, was diagnosed with MS 3 years ago. She hasn't taken part in a helminthic therapy trial but says she would have no problem doing so.
"The idea makes me feel a bit squeamish but, hey, I inject every day, and I don't really know what I'm injectingit's some chemical drug that I don't really know what it is, how it works. But I do it every day. And actually, a worm feels a bit more natural. I understand what a worm is!"
HEALTH
JUNE 28, 2011, 3:46 P.M. ET
Parasitic Worms May Offer Hope on MS
By STEN STOVALL
For people suffering from debilitating autoimmune disorders such as multiple sclerosis, there is growing evidence that help may be at hand from an unusual source: parasitic worms.
In a U.S. study, early safety tests suggested the eggs of pig whipworms have anti-inflammatory properties, reducing the size of brain lesions in MS patients. A similar trial is under way in Denmark. And in Britain, academics at the University of Nottingham are studying the potential health benefits of hookworms, another type of parasitic worm.
If these trials prove successful, treatment with parasitic wormsknown as helminthic therapycould provide a simple, cheap, natural and controllable treatment for the debilitating condition, which affects 2.5 million people world-wide.
Multiple sclerosis is an inflammatory disease of the brain and spinal cord, in which an overactive immune system attacks the nerve fibers responsible for sending signals to the rest of the body. Its symptoms include impaired vision, muscle weakness and spasm, fatigue, memory loss and depression.
Medication can slow the disease's progression, but many of the drugs on the market have unpleasant side effectsincluding hair loss, muscle aches, fever and nausea, sleeplessness and flu-like symptomsor more dangerous risks including organ damage and brain infection.
The market in MS drugs was worth about $12.6 billion in 2010, according to research firm Espicom. Top-selling Copaxone, an injectable treatment made by Teva Pharmaceutical Industries Ltd., generated $3.3 billion in sales that year.
Interest in helminthic therapy surged in 2007 with the publication of a study in Argentina by physicians Jorge Correale and Mauricio Farez. It showed that the progression of multiple sclerosis was much slower in patients who carried parasitic worms in their intestines than in those who didn't.
A study recently published in the Multiple Sclerosis Journal suggested the pig parasite Trichuris suis ova whipworm, which lives in the host's intestine, is effective in treating MS symptoms.
"The results are quite promising," says John Fleming, a professor of neurology at the University of Wisconsin School of Medicine and Public Health, who led the study.
Five patients took part in the Phase 1 trial, called Helminth-Induced Immunomodulation Therapy, or HINT. All were newly diagnosed with relapsing-remitting MS, a form of the disease in which new symptoms can appear and old ones resurface or worsen.
Whipworm eggs were taken from disease-free pigs and grown in Denmark in a clean environment by a German biotech company, OvaMed GmbH. Every two weeks over the course of three months, the patients in the study drank 2,500 of the eggs mixed into a sports drink. The eggs hatched in the patient's intestines and were killed by the immune system after about a week.
Patients who took part said the liquid was salty but didn't taste or smell unpleasant.
"It was like drinking a shot of salty wateryou didn't notice the worms. It wasn't like there was anything chunky in it," explains Jim, 40, the first patient recruited for Dr. Fleming's safety study, who asked not to have his surname published.
"I signed up shortly after being diagnosed and didn't have a problem with it because I was pretty scared and, for me, ingesting worm eggs is just not a big deal."
During the HINT study, patients underwent MRI scans, which tracked the number of new brain lesions that developed before, during and after they ingested the worm eggs.
"What makes us optimistic is that brain lesions in four out of the five patients decreased over the course of the study and then reboundedor roseagain after it finished," says Dr. Fleming. While the pattern shown by the MRIs is encouraging, he adds, larger and longer studies will be needed before any definite conclusions are possible.
Researchers say the Wisconsin study's findings could mean that the immune system's over-response to the brain tissue was lessened by anti-inflammatory effects from the worms, and this could offer an alternative approach to treating MS.
Dr. Fleming's HINT1 trial, which was funded by the U.S. National Multiple Sclerosis Society, will be followed by a bigger HINT2 study.
"We're now going forward and are midway recruiting 18 new MS patients for a Phase 2 trial that will last 10 months, with final results probably announced in around 18 months or so," he says.
In Britain, a similar study is being planned using parasitic hookworms. Funded by the U.K.'s Multiple Sclerosis Society and conducted by the University of Nottingham, the Phase 2 clinical trial, called Worms for Immune Regulation in MS, or WIRMS, will involve 70 patients.
"The worms will be administered to patients through applied arm patches, burrowing from there through the skin and giving a live infection," explains Doug Brown, head of biomedical research at the U.K. Multiple Sclerosis Society. After nine months, the worms are flushed out with a de-worming tablet called mebendazole. Patient recruitment starts this summer and the study's findings should be published in around three years' time, says Professor David Pritchard, the co-lead in the WIRMS study.
Prof. Pritchard, an immunologist-biologist, says that while the Wisconsin study uses worms found in pigs, "we're using a human parasite that lives only in people, and we believe it has advantages. We have worked with this parasite for decades, so we understand its biology."
As part of his investigation, Prof. Pritchard allowed himself to be infested with hookworms. He admits he was nervous at the time.
"Too many [worms] could cause tissue damage. And, once they are on the skin, there is no going back, until the worms reach the gut, from where they can be eliminated with worming medicine," he explains. He says he felt intense itching within seconds of the worms hitting his skin. "Thereafter," he says, "there was a feeling of intestinal discomfort as the worms grazed on the intestinal tissues."
Prospective patients need not be put off by Prof. Pritchard's experience, though. Whereas he was infected with 50 worms, patients in the study will receive lower doses. Following on from safety studies, 10-25 worms were chosen, because of the relatively asymptomatic nature of infection with lower doses.
Longer-term recipients of 10 worms report an easing of mild gut symptoms as host and parasite seemingly reach a form of biological agreement. "It is at this point that we hypothesize that immune regulation may be taking place, as the worms suppress the immune system to ensure their survival," he says.
Prof. Pritchard says the trial will assess whether the worms' presence can prompt the activity of a subset of the immune system's white blood cells, regulatory lymphocytes, which tone down the inflammation that causes allergies and autoimmune diseases.
The theory behind the HINT and WIRMS studies and others like them is known as "the hygiene hypothesis." This argues that developed countries such as the U.S., Europe and Japan have higher incidences of allergies and autoimmune diseases because the population has little or no exposure to parasites or infections.
In developing countries, where people are exposed to low-level infections or infestations, the rates of such diseases are much lower.
"If we get a sterile environment, like we have in Western countries for the last century by and large, an unintended consequence may be that the immune system develops in abnormal ways. That it may overreact against the patient's own tissues," explains Dr. Fleming, who led the Wisconsin study.
Alasdair Coles, a neurologist and researcher specializing in MS at the University of Cambridge, is aware of the planned WIRMS trials but isn't involved in them.
He says helminthic therapy is "potentially useful." It is "relatively cheap, relatively easy, relatively safe and all that matters is that we find out how efficacious it is."
But, he warns, the potential benefits may be overstated. "My prediction will be that this will be a safe but only partially effective therapy," he says. "The data that we have so far, which is very little, would suggest that efficacy is rather low; real, but rather low."
Shana Pezaro, a 32-year-old living on the south coast of England, was diagnosed with MS 3 years ago. She hasn't taken part in a helminthic therapy trial but says she would have no problem doing so.
"The idea makes me feel a bit squeamish but, hey, I inject every day, and I don't really know what I'm injectingit's some chemical drug that I don't really know what it is, how it works. But I do it every day. And actually, a worm feels a bit more natural. I understand what a worm is!"
