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    You are here : Home » MS Research News » Endo-parasites & 'Helpful' Organisms

    Endo-parasites & 'Helpful' Organisms

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    Recruitment starts on Multiple Sclerosis hookworm trial

    HookwormParasitic worms could offer a new treatment hope for patients suffering from the autoimmune disease multiple sclerosis, scientists believe.

    Academics at The University of Nottingham have begun recruiting people suffering from the neurological condition on to a trial that will see them infected with a low, harmless dose of the helminth parasite Necator americanus — or hookworm.

    The scientists are hoping to prove that the presence of hookworms in the body switches off the mechanism by which the body's immune system becomes overactive — the main cause of MS — and can reduce both the severity of symptoms and the number of relapses experienced by the patients.

    The study is being led by Cris Constantinescu, Professor of Neurology in the University's School of Clinical Sciences and a leading MS expert, and David Pritchard, Professor of Parasite Immunology in the University's School of Pharmacy, who has spent decades studying the biology of the hookworm.

    Professor Pritchard said: "This study appears counter-intuitive — we are introducing a parasite which is by definition harmful, to act as a stimulus to moderate disease. As a safeguard the hookworms are being used in carefully controlled and monitored conditions, and if successful could herald a much-needed therapy for MS patients.

    "Currently, there are many MS patients for whom conventional medicines are ineffective or are associated with unwanted side effects. Hookworms have an innate ability to moderate the immune system to allow them to survive in the body for years. This moderation may have a bystander effect on the progression of MS."

    The study team is in the process of recruiting more than 70 patients from the Nottingham and Derby areas who suffer from the most common type of the disease, relapsing remitting MS (RRMS), in which patients symptoms such as vision problems, dizziness and fatigue, appear and then fade away either partially or completely, and secondary progressive MS with superimposed relapses.

    Half of the patients on the trial, funded with £400,000 from the MS Society, will receive a low dose of the hookworms —25 of the microscopic larvae — on a plaster applied to the arm, while the other half will receive a placebo plaster.

    Once the larvae come into contact with the skin they work their way through into the blood stream until they reach the lungs where they are coughed up and swallowed to get to their final destination, the gut, where they survive by latching on to the gut lining and feeding on the host's blood. The worms do not multiply in the host but reproduce by producing fertile eggs, which are expelled in faecal matter. These hatch into infective larvae outside the body, and are used to infect patients.

    The patients on the study will be given regular blood tests to check they are not anaemic — a sign that the dose of hookworms could be too high for that individual. Prior safety studies indicate that this is unlikely to happen, and de-worming will take place if it does.

    At the beginning of the trial, the participants will undergo a MRI scan to record the scarring or lesions on the brain which are present in MS patients. Over the course of nine months, all the patients will be scanned on a regular basis for new or worsening lesions which can be a tell-tale sign of relapse.

    At the end of the trial, the results of the two patient groups will be compared to establish whether the hookworms have been successful in damping down the immune system of the patients, keeping their symptoms in check and preventing relapses.

    Professor Pritchard has been studying hookworms for almost two decades since his work as a zoologist took him to remote villages in Papua New Guinea to investigate the parasites in the indigenous population.

    Evidence showing that natural parasitic infection led to a lower incidence of other immune-related diseases such as allergy prompted research into the therapeutic potential of worm infection.

    Before they were able to put the worms into clinical trial to test their efficacy against human disease, the team needed to establish they were safe to use and had no ill effect while passing through the lungs.

    Initially, the researchers volunteered to be infected themselves to establish a safe dosage at which there were no side effects, before participants suffering from asthma and rhinitis were recruited to clinical trials in which they were infected for a period of 12 weeks and studied to ensure there was no effect on respiratory function as parasites migrated through the lungs.

    Following the successful outcome of the safety trials, the team has undergone the necessary process of having the hookworms approved as an investigational medicinal product by the Medicines and Healthcare Products Regulatory Agency (MHRA).

    Source: PhysOrg.com © PhysOrg.com™ 2003-2012 (01/03/12)

    Parasitic worms may offer hope on MS

    Parasitic WormsFor 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 worms—known as helminthic therapy—could 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 effects—including hair loss, muscle aches, fever and nausea, sleeplessness and flu-like symptoms—or 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 water—you 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 rebounded—or rose—again 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 3½ 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 injecting—it'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!"

    Source: The Wall Street Journal Copyright © 2011 Dow Jones & Company, Inc. (29/06/11)

    Out of the shadows: our unknown immune system

    Hook wormDeliberate infection with a blood-sucking worm seems an odd way to treat multiple sclerosis (MS).

    Yet more surprising is what this experiment may tell us about a "shadow" branch of our immune system. Completely unknown until recently, this is pointing to new ways of treating a host of complex diseases.

    A couple of recent studies suggest that parasitic infection dampens inflammation and reduces relapse rates in people with MS, in which the body's own cells are attacked by the immune system as if they were "foreign". So Cris Constantinescu at the University of Nottingham, UK, and his colleagues plan to place tiny hookworm larvae on the skin of 32 people with MS, allowing the worms to burrow down and infect the volunteers.

    The team won't just be looking for a reduction in volunteers' symptoms though. They will also be watching to see if the parasites boost numbers of a set of newly discovered immune cells, known as regulatory B cells (B regs).

    B regs are sending shockwaves through the immunology community. Until recently it was assumed that B cells' main role was to make antibodies at the behest of T-cells. These master regulators enhance or suppress an immune attack depending on the situation, as well as carrying out immune attacks in their own right. It was therefore thought that T-cells are at fault when the body attacks itself in autoimmune diseases, such as MS, asthma, diabetes and rheumatoid arthritis - and when it fails to route out disease agents, such as cancer cells.

    Now it seems that T-cells are not the immune system's only regulators. Experiments suggest that under some circumstances, B regs regulate T-cells, providing a shadow role for B cells.

    "Diseases we've traditionally thought to be mediated by T-cells might actually be regulated by B cells," says Kevan Herold of Columbia University in New York. Boosting B regs might therefore provide new opportunities for treating autoimmune diseases, while inhibiting B regs it could be a new way to treat cancer.

    Animal studies are already suggesting that the approach might work in one type of asthma. In a study published in May, Padraic Fallon of Trinity College, Dublin, and his colleagues isolated B regs from the spleens of mice infected with the parasite Schistosoma mansoni. When they transferred the B cells into mice primed to develop asthma, this either reduced their symptoms or stopped them developing asthma in the first place (The Journal of Allergy and Clinical Immunology, DOI: 10.1016/j.jaci.2010.01.018).

    "These are major regulators of the immune system in allergic disease," Fallon concludes. B regs seemed to work by releasing a chemical called IL-10 into the lungs, drawing in regulatory T- cells (T regs), which in turn inhibited immune attacks.

    IL-10 played a similar role in a subset of B regs, which Thomas Tedder at Duke University School of Medicine in Durham, North Carolina, calls B10 cells. His team found that transferring these cells into mice with a disease similar to multiple sclerosis reduced the severity of disease.

    Tedder has also identified similar cells in humans. "We can stimulate them and we can isolate them, but they're fairly rare," he says. He presented both findings in May at the annual American Association of Immunologists meeting in Baltimore, Maryland.

    The race is now on to identify drugs that might boost B regs in people with autoimmune diseases or suppress them in people who have cancer.

    One clue that such an approach might work comes from studies of rituximab, which kills B cells. First prescribed for the treatment of B cell lymphoma, a type of cancer, the drug has also reduced symptoms in people with diabetes, MS and rheumatoid arthritis. Rituximab most likely knocked out all the B cells to start with, and then, for some reason only the B regs grew back, which helped suppress autoimmunity, suggests Frances Lund of the University of Rochester Medical Center in New York (Nature Reviews Immunology, DOI: 10.1038/nri2729).

    In individuals with cancer, however, it might be desirable to suppress B regs. Preliminary evidence suggests that as well as keeping autoimmunity in check, B regs also help dampen the immune system's natural ability to recognise and destroy tumours.

    Tedder's team has already created antibodies that can deplete B10 cells - but not other B cells - in mice, and says he has similar antibodies that may selectively deplete human B10 cells - although he hasn't yet tested them in people.

    Arya Biragyn of the US National Institute of Aging, and his colleagues, also announced at the Baltimore meeting that they have identified a separate set of B regs that cancer seems to recruit in order to avoid detection by the immune system. Destroying these cells might make let's hope you have deep pockets cancer immunotherapies work better.

    "Even if you transiently wipe out B cells during immunotherapy, this should give you very potent anti-tumour responses against hidden tumour cells," Biragyn says.

    Working out how parasitic worms trigger B reg activity might suggest additional ways to do this - and to boost B regs. Indeed, Fallon has identified several molecules released by parasitic worms that seem to trigger B regs.

    Until such drugs are developed, parasites might be the best way to boost B regs. Severe hookworm infection can cause malnutrition, internal bleeding and anaemia, but in a mild and controlled infection, the dangers are minimal, says Constantinescu, though there may be some itchiness as the worms go through the skin.

    Source: New Scientist © Copyright 2010 Reed Business Information Ltd (04/06/10)

    Gut instinct: the miracle of the parasitic hookworm

    Hook WormsThere are hard sells and there are hard sells.

    "If I were a charlatan," Jasper Lawrence tells me, "I would be flogging flower essences or herbal supplements."

    He would not, I guess it is fair to say, be trying to market over the internet "blood-sucking parasitic worms that live in your gut for five years".

    And neither, he argues, would he have lately left behind his home in California, his children and his friends, and gone on the run from the American authorities in order to stay out of prison and in business (for the 180 clients who rely on him). If Jasper Lawrence is not a charlatan, then, he is at least a man on a high-risk mission.

    As one of the proofs of that mission, Lawrence – an intensely articulate and bright-eyed 46-year-old – has only to point to the location of our interview. We are sitting in a cottage garden on the southern edge of Dartmoor, and in the afternoon sun the air is thick with spring pollen. In previous years, Lawrence says, he would not have been able to talk out here for five minutes without succumbing to the chronic hay fever and seasonal asthma that have afflicted him nearly all his life. The only reason he can now, he suggests, is that out here on the patio we are not alone. Also in attendance, in Lawrence's small intestine, are 50 hookworm (Necator americanus), which are, he believes, not only his livelihood but also his saviours.

    Jasper Lawrence's journey to this curious belief began in this house – which belongs to his aunt – nearly six years ago. He was living at the time in Santa Cruz, California, his marriage was on the rocks, and he had come here on holiday with two of his five children. It had been a while since he had seen his Aunt Mary – who had informally adopted him as a teenager – and when she opened the door to him, she could not hide her shock.

    Lawrence, a wiry man, had gained nearly four stone. The weight gain was a symptom of his reliance on the oral steroid Prednisone, which, at the time, he says, was his only defence against the asthma that left him constantly breathless. His inhalers did not work, he had to rest halfway up a flight of stairs, he could no longer play with his kids. By chance, his aunt had recently heard a BBC radio documentary about the possibilities of parasitic hookworm as a treatment for allergies, and she mentioned the programme to Lawrence. He subsequently spent all night trawling the internet, reading research, following links, and by the morning was convinced that there was only one way he could cure himself: he needed parasites.

    The research that so excited Lawrence was a development of the so-called "hygiene hypothesis". This theory, first developed by David P Strachan in the British Medical Journal in 1989, suggests that many of the "modern" illnesses that have grown exponentially in industrialised western countries – allergies, asthma, type 1 diabetes, Crohn's disease, irritable bowel syndrome, multiple sclerosis and possibly rheumatoid arthritis and autism, and others – are the result of inappropriate autoimmune responses. The development of chlorinated drinking water, vaccines, antibiotics, and the sterile environment of early childhood have, the argument goes, as well as preventing infection also upset the balance of the body's internal ecology. Inflammatory responses that evolved through millions of years in the certain presence of "old friends" – parasites and bacteria – have been thrown wildly out of kilter in their absence, causing autoimmune illnesses, in which the body's immune system turns on itself, and oversensitivity to harmless antigens such as pollen, or dust, or cats, or particular food groups.

    The story that most interested Lawrence was the ongoing research of Professor David Pritchard, an immunologist at Nottingham University. While in the field in Papua New Guinea in the late 1980s, Pritchard noted that patients infected with the Necator americanus hookworm were rarely subject to the whole range of autoimmune-related illnesses, including hay fever and asthma. In the years since, Pritchard had developed a thesis to support this observation through painstaking clinical trials (which began after he infected himself with 50 hookworm). The thesis proved that hookworm, in small numbers, seemed able to regulate inflammatory immune responses in their hosts. (Dr Rick Maizels, at Edinburgh University, has subsequently identified the process – involving the white T-cells in the blood that regulate immunity – that allowed this to happen.)

    "When I read that stuff," Lawrence recalls, "everything immediately made sense to me. In our obsession with cleansing and sterility, with the eradication of parasites, we had thrown the baby out with the bath water. The central idea is that our bodies have an internal ecosystem. One of the ironies of this, to me, is that everyone is concerned about biodiversity in the outside world, and saving the rainforest, but we've also screwed up the biodiversity inside us."

    And so Jasper Lawrence set out on what became a compulsive and somewhat desperate quest. Despite the fact that perhaps one billion people in the world still live with hookworm, getting infected in the developed western world is not an easy thing. The drift of our culture has long been to eradicate parasites – or "symbions", as Lawrence prefers. To begin with, he tried to get accepted as a participant on one of the various studies investigating the phenomenon. But when that proved fruitless he determined to go to Africa and become infected.

    Prior to this trip, he recalls, he contacted "all the clever people I knew who worked in medicine. I sent them all the research and asked them their opinion. They all said the same thing: 'Yes, it appears safe, but I would not advise you to do this; you need to wait 20 or 30 years for all the studies to come in. For a molecule to be identified and a drug to be tested…'"

    You don't have to talk to Lawrence for long to realise he is not a man who might be prepared to wait 20 or 30 years for anything. Instead, he took a plane to Cameroon.

    The life cycle of Necator americanus is not an attractive one. Hookworm infiltrate a new human host when larvae, hatched in human excrement, penetrate the soles of the feet, enter the bloodstream, travel through the heart and lungs and are swallowed when they are coughed up from the pharynx. Only in the small intestine do they mature into adults (just under 1cm long), where they can live an average of five years latching on to the intestinal wall, siphoning off tiny amounts of blood, and – this is the crucial part – "regulating the volume" of immune responses. They mate inside the host, with females laying up to 30,000 eggs per day, up to 50m eggs during a lifetime, which pass out in faeces. In the tropics, in places where there is an absence of both toilets and shoes, extreme cases of hookworm kill 70,000 people a year, and afflict many others with anaemia; they exacerbate malnutrition and stunted growth in children. There are crucial caveats to these scare stories, however. Hookworm cannot and do not replicate in the gut. They are not infectious. In small numbers they are considered harmless, and very easily eradicated. And their life cycle is fatally interrupted by the introduction of either shoes or plumbing.

    Lawrence is a practical man, and he weighed up the risks. In Cameroon he spent a couple of weeks travelling to remote villages, discovering where the local latrines were and wandering around the area without shoes.

    What did the people make of this behaviour? "Typical reactions would range from being laughed at – what's that idiot doing walking round where I take a shit? – to anger: a lot of them were convinced I was there to steal some aspect of their essence. I got shaken down a lot."

    He did have doubts. When he had told friends what he was going to do, they freaked out. Because his journey coincided with him having left his wife, people thought he was having a crisis or a breakdown. "You can't help but be a bit scared," he says. "The big fear was that I'd come back with the wrong disease, river blindness or elephantiasis, or Dengue fever, or whatever. On the other hand I had seen exactly how my life had declined in the last five years with asthma. Modern medicine seemed to have nothing to offer me except palliative drugs. So really, I felt there wasn't a choice for me." Disgust was hard to overcome. "I was only able to take my shoes off the first time because I couldn't face going back and telling people I hadn't been able to do it."

    When he returned to Santa Cruz from Africa, Lawrence did not know if he had come back alone. "I hadn't seen any benefits after a few weeks, though I had some symptoms," he says. "After six or eight weeks you will have embryos in your faeces, so I packaged up my samples and sent them off to the lab, and I got a negative. What I didn't realise was that because American labs never see parasites, they don't know what they are looking for."

    Then, he recalls, one day in the spring he was out driving and he made what for him would ordinarily have been a huge error. "I had the window of my car rolled down," he says. "Normally if I did that at the start of spring I would spend the rest of the day blowing snot, swollen red eyes, the works. But it didn't happen."

    The acid test was cats. Lawrence was so allergic to cats that if he touched one and touched his face he would get a red mark. His eyes would swell shut. "So I deliberately exposed myself to a cat, which wasn't difficult because my ex-wife had decided to favour cats over my health. So I went to her house and petted the cat. And nothing happened." In that moment, Lawrence's fate was sealed. "I had known," he says, "that if it worked the way the science suggested it would, I would have to try to get that knowledge out to the world."

    Lawrence does not have a conventional background as a medical pioneer. His childhood was characterised by insecurity. His father was a "brilliant and disturbed" systems analyst in the early days of computing and his parents moved to New York from England in 1968, in search of the summer of love. They split up and Lawrence roved around the States with his hippy mother and her sometimes violent boyfriend until, at 14, he persuaded her to let him escape to the stability of England and be taken in by his aunt. He was identified as a gifted child but he never fulfilled that potential, dropping out of his Oxbridge group in hard sciences, dabbling in drugs.

    At 19 he took himself back to America, got a job digging irrigation ditches, sold second-hand cars for a while, and eventually, having married, set up his own advertising agency serving Silicon Valley clients: "I was in the right place at the right time for the dotcom thing – so I made a ton of money, hired 30 people, and then lost all the money and fired them again." The experience served him well. Before he set up his business selling worms (Autoimmune Therapies) the salesman in Lawrence recognised there might be challenges. "You have to bear in mind that buying a blood-sucking intestinal parasite off a stranger without a college deg-ree over the internet is not most people's first choice of remedy. People come to us when they are desperate."

    Several of the people who came originally had been involved in clinical trials with hookworm or whipworm (Lawrence prefers to call them "helminths") and were among those who had seen their symptoms – of Crohn's or hay fever or multiple sclerosis – go into lasting remission. Lawrence makes startling claims about his cohort of clients: that all 15 of the people he "treats" for multiple sclerosis are in remission, for example. The claims are impossible to verify, though there is an open and extensive online forum for users of the therapy, and the people I later speak to – a former headmaster from Nottingham, John Scott, for example, whose allergies were so bad that he was living on powdered food supplements and now reports a near normal diet – certainly support a degree of both Lawrence's evangelism and his frustration that the findings are not more widely known and studied.

    "You have all this and no one is making a move on it?" he asks from time to time. "I mean, am I the only fucker on the planet reading this science? I'm not. All the drug companies know about it. But there is a huge disincentive for them to do anything about it. You can't patent a hookworm."

    Lawrence is, of course, his own factory farm. "All I have to do," he says, "is recreate the tropics in a container, give the helminth something clean to migrate through, so you don't have to come anywhere near human excrement, then pick them off the surface of that, wash them repeatedly in various antimicrobials and antibiotics, and then package them up in sterile liquid and they are ready to go. They will live about a month like that. They are delivered to clients as a patch, and they go from there." He sells five years of treatment – with extensive support services – for $3,900, a figure he justifies with the comparative cost of MS drugs for example, which might be closer to $150,000.

    For three years Lawrence's business was growing slowly and, to judge from the thousands of postings on the internet forums, with an almost universally positive response. Then, last November, the US Food and Drug Administration (FDA) knocked on his door in California. Lawrence's helminths could variously have been classified as a vaccine or a medical device (into which category fall increasingly widely used maggots and leeches) or a pharmaceutical. "To our misfortune," he says, "an unknown bureaucrat decided to classify it as a pharmaceutical."

    To begin with, because there had been no complaint about Lawrence's service from any of his clients, the FDA agent suggested he only needed to bring his website into compliance. The mood, however, changed on a second visit. "The agent was clearly uncomfortable being there because he knew what was going to happen to us," Lawrence says, running through a list of possible outcomes that included, he believes, in comparable cases, "Swat teams in the morning, detention before trial, million-dollar fines, prison sentences, blacklisting. This is the first week of November. I decided on the spot we had no option but to leave."

    He and his new partner Michelle, who he had known since teenage days in Devon, made this decision in part because they feared for their liberty, but also because he felt he had a duty to his mission. "For three years I had been listening to a tiny trickle form this great torrent of human misery that is brought about by autoimmune disorders. And I believe we had a solution."

    The FDA left at 5.30pm on a Friday, promising to return on the Monday. By 1am on Saturday Lawrence and Michelle were walking across the border into Mexico at Tijuana – where he knew there was no passport control – holding hands. "I had scraped $6,000 together largely by running out on our rent, got a couple of backpacks, some sleeping bags, sensible shoes and a mosquito net. We went two days without food. Took a 36-hour bus to Guadalajara, stayed in a hotel which turned out to be a whorehouse. We eventually calmed down enough to get a plane to Cancun, and a bus to Belize, and made our way back to Britain."

    He still does not know if his paranoia was justified. The FDA is continuing its investigation but will only inform him of the charge if he appears in person. He continues to move around Britain and won't disclose his address; he talks eventually of hiding out in Central America, directing his anger against the "system" which mitigates against his kind of therapy. "You know," he says, "if you watched late-night television in America and you were at all credulous you would believe that baldness, obesity and small penises could be cured with a pill. But as soon as you come up with something that does work, you are in an environment that is set up to deal with vast billion-dollar corporations with phalanxes of lawyers and researchers. Helminthic therapy could have been accommodated into the category of probiotic or supplement, like a live yogurt – it's the same principle. The organism is larger, but the numbers are way smaller."

    The pioneer of this potential therapy, Professor David Pritchard, at Nottingham University, is of course more circumspect about the possibilities. After a terse exchange of emails with Lawrence a couple of years ago he cut off correspondence. Having conducted positive trials with Crohn's disease and hay fever, however, and with an NHS-funded study under way to look at MS, Pritchard has suggested he understood the motivations of Lawrence's unregulated efforts and the demand out there for the therapy. But he does not appear to approve of Lawrence's business, and did not respond to interview requests for this article. He places his faith in the conventional means of identifying – and patenting – the molecular mechanisms that produce the response and has admitted he cannot envisage patients lining up at clinics to receive patches of parasites alongside vaccinations. "The worst-case scenario would be to cause damage," he has said. "I'm nervous about deliberate infection, but I feel the hypothesis should certainly be tested."

    Dr Rick Maizels at Edinburgh University is also at work on research into finding the "drugs from bugs" that will replicate the helminth effect, and other studies are ongoing across the world, in Brisbane, Denmark, Buenos Aires and elsewhere. Maizels sees no harm in Lawrence's efforts to short-circuit that lengthy and slightly unfocused process – "There seems little risk," he says, "in that we know low levels of hookworm are relatively harmless, but neither is it an open-and-shut case that the parasites will work in every or any patient." Maizels believes the hygiene hypothesis behind this effect is gaining wider credence, and is certain that helminths have the ability to "calibrate the autoimmune response" but says that "how much they turn it up and down, and how precisely they do it, is still to be discovered. There may yet be adverse response. The fact is we do not know." That knowledge will only begin to be revealed "in a decade or more of trials".

    Creating another drug, however, will not, to Jasper Lawrence's fertile mind, represent a solution. It is the live aspect of the therapy that he believes gives it its efficacy. If scientists really believe the hygiene hypothesis he argues, then what they need to be investigating is not the lucrative possibility of a patented formula, but the ways in which the public might be educated in the idea of co-evolution, our symbiotic relationship with our internal fellow travellers. Lawrence is nothing if not an idealist. "When I was 17 I read The Selfish Gene," he says. "I needed a framework, a philosophy to describe the universe to me. I considered religion for a while, but The Selfish Gene delivered. Once you realise we are vessels for our genes, then all sort of things follow." The logic of his therapy, he argues, is one of them. "If it is allowed to develop, the use of benign organisms could be as big as antibiotics. Well-baby checkups, if I succeed, will include deliberate infection with a variety of protozoa and bacteria and helminths starting at age two, because the effect of these things in a child seems profound…"

    He veers quickly from that hope to the reality of his situation, however. The imagined education process will, he knows, always be dogged by the fact that our cultural norms are very anti-parasite and worm, and that is partly because in their most extreme forms they make for great television. "I understand how the world works, but I am still angry. An enlightened country could easily do a crash programme to test this, and the benefits and savings would be immense… The truth is, though, I think I am going to be discredited by the media or marginalised by the law, and the idea will be snuffed out."

    It won't be for the want of trying. The previous weekend Lawrence and Michelle had been to a wedding at which the bride had recently been diagnosed as having multiple sclerosis. Inevitably, Lawrence took on the role of the Ancient Mariner, telling his story to anyone who would listen. Their wedding present was 50 hookworm. Surprisingly or not, the bride returned it unopened.

    Source: guardian.co.uk © Guardian News and Media Limited 2010 (23/05/10)

    A new prescription - parasite eggs

    Intestinal WormsWhipworms are two-inch-long parasites that sicken pigs by burrowing into their guts.

    Scientists, however, are beginning to appreciate them for their curative power in humans.

    Large-scale trials underway in Europe are testing whipworm eggs as a treatment for autoimmune diseases such as Crohn's, a digestive ailment, and multiple sclerosis.

    About 23.5 million Americans have some type of autoimmune disorder. "This is probably the biggest market in the entire history of medicine," says Detlev Goj, founder of Ovamed, a German biotech. He believes whipworm eggs may prove effective against as many as 60 diseases.

    Goj, who in 2002 got European regulators to approve the use of maggots to clean wounds, became interested in whipworms after coming across a 2005 study in which 21 out of 29 patients with Crohn's disease went into complete remission after being dosed with the parasite's eggs. The data seemed to support the "hygiene hypothesis," which holds that people have become too clean for their own good.

    The thinking is that parasites may act on the immune system by boosting the T-cells that help identify and kill infectious agents. When those cells don't work properly, substances and tissues normally present in the body can be mistakenly targeted, causing a range of disorders. "Now that we've eliminated parasites in many Western countries," says Goj, "the immune system doesn't get the required challenge anymore."

    Ovamed has supplied sterilized batches of whipworm eggs for human trials for Crohn's disease, multiple sclerosis, peanut allergies, and for symptoms of autism. One of Goj's partners is Asphelia Pharmaceuticals. That San Diego (Calif.)-based company is projecting peak annual sales of about $2 billion in North America for its treatment for Crohn's.

    But what about the yuck factor? Will people willingly infect themselves with worms under doctor's orders? Goj, whose company is conducting phase two trials in Crohn's disease at 40 medical centers in Europe, does not anticipate any resistance. "The eggs of the whipworm are so small they're hard to find on a microscope," he says. "All you see is a small cup of water." And since the worms don't reproduce in humans, the parasites are gone in about two weeks.

    Whipworms aren't the only invertebrates commanding attention. A 2007 study in Argentina found that MS patients who were infected with Schistosoma mansoni, a parasite found in water supplies in poor countries, suffered fewer relapses than those who were not. An immunologist at the University of Nottingham has been looking into whether pin-sized hookworms may protect against asthma, Crohn's, and MS.

    The bottom line: Parasites are being used to treat autoimmune diseases. Some researchers believe people can be too clean for their own good.

    Source: Bloomberg Business Week ©2010 Bloomberg L.P. (21/05/10)

    Can dirt do a little good?

    DirtInfants are enchanting all over the world, as the new movie "Babies" shows. But their standards of hygiene sure vary.

    The film captures the first year of life for four diverse babies. In a nomadic family in Namibia, Ponijao drinks from muddy streams, chews on dry bones and uses her many siblings' body parts as toys.

    On a small family farm in Mongolia, a rooster struts around little Bayar's bed, a goat drinks from his bathwater and livestock serve as babysitters.

    By contrast, Mari, growing up in high-rise, high-tech Tokyo, and Hattie, whose doting parents live a "green" lifestyle in San Francisco, both have modern conveniences and sanitation.

    Statistically, Mari and Hattie are healthier. Some 42 out of 1,000 children in Namibia, and 41 out of 1,000 in Mongolia die before their 5th birthday; compared with only 8 in 1,000 in the U.S. and only 4 in Japan.

    Yet the upscale urban infants are at higher risk for some health problems—including allergies, asthma and autoimmune diseases like Type 1 diabetes, multiple sclerosis and inflammatory bowel disease—than the babies in the rural developing world.

    While the film makes no mention of hygiene in any of the countries, its images evoke an intriguing medical controversy: Are we too clean, with our preoccupation for hand-sanitizers, disinfectants and anti-microbial products? Now, there's research that suggests there may be a way to get the best of both worlds.

    "We seem to be healthier, but we have traded one problem for another problem," says Joel Weinstock, chief of gastroenterology/heptology at Tufts Medical Center in Boston. Using the premise that exposure to a certain amount of dirt and germs carried by livestock may help the body build up resistance to disease, Dr. Weinstock is one of the lead researchers behind clinical trials using pig whipworm eggs to treat peanut allergies, MS and other autoimmune diseases.

    According to the "hygiene hypothesis," first proposed in 1989, exposure to a variety of bacteria, viruses and parasitic worms early in life helps prime a child's immune system, much like sensory experiences program his brain. Without such early instruction, the immune system may go haywire and overreact with allergies to foods, pollen and pet dander or turn on the body's own tissue, setting off autoimmune disorders.

    Many of these microorganisms evolved symbiotically with humans over millions of years—the so-called "old friends" theory. But where they've been eradicated, a key part of human development has been thrown off.

    "The vast majority of microbes are harmless. There are only a few dozen that can cause lethal infections," says Thomas McDade, director of the Laboratory for Human Biology Research at Northwestern University.

    Allergies and autoimmune diseases were virtually unknown in the U.S. before the turn of the last century, but they began to emerge as modern sanitation, decontaminated water, food refrigeration and antibiotics became more widespread. "There's a whole series of diseases that just emerged in the 20th century," says Dr. Weinstock.

    In 1998, about 1 in 5 children in industrialized countries suffered from allergic diseases such as asthma, allergies and rashes, according to the International Study of Asthma and Allergies in Childhood, a global research initiative. The incidence of peanut allergy in the U.S. tripled between 1997 and 2008, according to a report from Mount Sinai School of Medicine in New York.

    But such diseases are still relatively rare in Africa and rural Asia, as are Type 1 diabetes and multiple sclerosis.

    "The geographical distribution of allergic and autoimmune diseases is a mirror image of the geographical distribution of various infections diseases," says a report by French researchers in a March issue of the journal Clinical & Experimental Immunology devoted to the hygiene hypothesis.

    Exposure to immune-stimulating germs may also lower the risk of heart disease, according to Dr. McDade. In a study of 1,700 Filipinos followed from birth to age 21 published this year in the journal Proceedings of the Royal Society, those who grew up around chicken, pigs and dogs and had bouts of diarrhea in childhood had lower rates of C-reactive protein, an inflammation marker that has been linked to cardiovascular disease, as young adults.

    There are other dangers lurking in muddy water and animal feces. Nearly 70% of the 8.8 million deaths of children under age 5 worldwide in 2008 were caused by infectious diseases, most frequently pneumonia, diarrhea and malaria, according to an analysis in the Lancet last week.

    Even though rural Africa and Asia have made enormous strides in public health in the past decade, infant mortality stands at 31 per 1,000 in Namibia and 34 per 1,000 in Mongolia, compared to 7 per 1,000 in the U.S. and 3 per 1,000 in Japan.

    In Namibia, about one-quarter of children have stunted growth related to poor nutrition; about 120,000 children have lost one or both parents, predominantly to HIV/AIDS, and 26% of all women aged 15 to 49 have had at least one child die.

    "Living more sanitarily may have increased asthma, but in terms of scale and impact, that's tiny compared with the benefit of not dying from disease for lack of hygiene," says Michael Bell, an infectious disease specialist and deputy director of Healthcare Quality Promotion at the Centers for Disease Control and Prevention.

    Some scientists are searching for ways to harness the immune-priming effects of microorganisms without the fatal diseases. Parasitic worms known as helminthes are leading the way.

    Clinical trials are under way in the U.S. and Europe testing Trichuris Suis Ova (TSO)—-a species of pig whipworm—as a treatment for peanut allergies, ulcerative colitis, Crohn's disease and MS. A study is being designed to test it with asthma. It's also being tested with adults who have autism, which some researchers believe could be related to immunological function.

    Preliminary studies seem promising: In one, when 29 patients with Crohn's disease, a disorder of the digestive tract, were given TSO every three weeks for six months, symptoms improved in 21 of them with no adverse side effects.

    The ova are suspended in a liquid, invisible to the naked eye. "There's no taste, nothing to feel," says Dr. Weinstock, one of the early developers who could share in the proceeds if TSO proves successful. The microscopic eggs hatch into microscopic whipworms in the gastrointestinal tract, which interact with the host's immune system and can dampen an overactive immune response, he explains. To date, there have been few side effects, he says. "As far as we know, this agent doesn't cause diarrhea," he adds. "Nothing crawls out of you."

    For those who fear the "ick" factor, Dr. Weinstock notes that even under normal conditions, people are teeming with microorganisms, which outnumber human cells by about 10 to 1, many of which are necessary for human health. Many foods—from yogurt to cheese to bread—also contain live bacteria and fungi.

    Some daily products now widely advertise that they contain probiotics, or good bacteria. But most immunologists say that those in food products have not been sufficiently studied or standardized to draw scientific conclusions about what health benefits they provide.

    Scientists are still working on ways to separate good germs from bad ones; in the meantime, they have a few insights: Studies have shown that children who grow up with household pets have fewer allergies and less asthma than those who don't.

    The CDC's Dr. Bell says that people should be vigilant about wound care since bacteria can cause problems if it gets into the blood stream, and he still advocates hand-washing. "If you're not doing it 10 times a day, you're probably not doing it enough," he says. But he and other experts say that regular soap and water are fine in most cases. Sterilizing hands is critical mainly for health-care workers and in hospitals, where disease-causing germs are prevalent and can easily spread.

    Many experts advise common sense. "We don't want to say to children, 'OK, play by the dirty river bank and catch whatever you can,' " says Dr. Weinstock. "But we can say there's nothing wrong with kids playing in the dirt. They don't have to live in total sanitation, and they won't die from eating something off the floor. It's probably more healthy than not."

    Source: The Wall Street Journal Copyright ©2010 Dow Jones & Company, Inc. (18/05/10)

    Parasitic worms may lead to treatment for multiple sclerosis

    Intestinal Worms

    Scientists from The University of Nottingham will study the potential health benefits of parasitic worms as part of a study investigating treatments for people with the autoimmune condition multiple sclerosis (MS).

    It is thought that hookworms may play a role in damping down the immune system, which is overactive in people with MS, the most disabling neurological condition in young adults.

    The £400,000, three-year project funded by the MS Society, aims to determine whether infection with a small and harmless number of the worms can lead to an improvement on the severity of MS over a 12 month period.

    If the trial is successful, the worms have the potential to provide a simple, cheap, natural and controllable treatment for MS.

    The WIRMS (Worms for Immune Regulation in MS) study is led by Professor Cris Constantinescu and Professor David Pritchard and is a randomised, placebo controlled, phase 2 study in people with relapsing remitting MS and will be carried out at multiple centres up and down the country.

    The 25 worms are microscopic and are introduced painlessly through a patch in the arm. They are then flushed out after nine months.

    Professor Constantinescu, said: "People are really interested in this form of potential therapy because it's a natural treatment. It's been tested for safety and we now need to study the potential benefits and any side effects."

    Jayne Spink, Director of Research at the MS Society said: "It sounds like science fiction, but it has been shown in a previous small study that people with MS who also had gut parasite infections had fewer relapses.

    "Over time, parasitic worms have evolved to be able to survive an immune system attack and have been linked to a reduction in the severity of the symptoms of MS, which can be debilitating.

    "If the theories can be shown to be accurate, using hookworms as a future treatment option may prove to be science fact."

    MS affects around 100,000 people in the UK and several million worldwide. Symptoms range from loss of sight and mobility, fatigue, depression and cognitive problems that often come on as attack - or relapses. There is no cure and few effective treatments.

    Dorothy Sutton, 58, from Awsworth, has lived with MS for 32 years and is a Helpline volunteer for the MS Society. She said that although the treatment sounded unusual, anything that could potentially to help alleviate the symptoms of MS is a positive step.

    "We have to explore every avenue of research to find treatments for MS. As long as it's safe and effective in helping the horrible symptoms, I don't think people mind where it comes from."

    The Division of Clinical Neurology at The University of Nottingham's Medical School is a strong research-led unit which draws heavily on its close relationship with people with MS to inform its work.

    Led by Professor Cris Constantinescu, the department features two academic and one NHS Neurology Consultants that are affiliated with the Neuroscience Directorate of Nottingham University Hospitals (NUH) NHS Trusts.

    Source: News-Medical.net © 2009 News-Medical.Net (04/03/09)

    Gut worms could treat Multiple Sclerosis

    Intestinal Worms

    Scientists are investigating whether gut worms can be used to treat or prevent conditions ranging from asthma and allergies to multiple sclerosis.

    Parasitic worms, or helminths, have largely been eliminated from humans in developed countries thanks to modern hygiene.

    But experts believe they could play an important role in regulating the immune system, and suggest their absence may be linked to increases in a range of disorders.

    Researchers are already looking at whether giving patients parasites can help to fight diseases.

    A trial in Nottingham involves infecting asthma sufferers with hook worms to see if their symptoms are eased.

    And US scientists are following up a study in Argentina which found that people with multiple sclerosis who naturally became infected with worms saw the progress of their disease slow.

    There are also hopes that drug companies will one day develop treatments that mimic the effects of worm infections on the immune system.

    Graham Rook, professor of medical microbiology at University College London, said there was an "evolved dependence" between humans and some parasitic worms.

    He said: "Certain organisms that were there throughout our evolutionary history have developed a role in causing the immune system to develop and causing the policemen of the immune system to be operating at the right level.

    "The modern changes in lifestyle - not just modern hygiene - starting in the early 19th century, have led to a gradual withdrawal of these organisms."

    Source: Channel 4 News © Channel 4 (30/01/09)

    Babies know: A little dirt is good for you

    Dirt and Immunity

    Ask mothers why babies are constantly picking things up from the floor or ground and putting them in their mouths, and chances are they’ll say that it’s instinctive — that that’s how babies explore the world. But why the mouth, when sight, hearing, touch and even scent are far better at identifying things?

    When my young sons were exploring the streets of Brooklyn, I couldn’t help but wonder how good crushed rock or dried dog droppings could taste when delicious mashed potatoes were routinely rejected.

    Since all instinctive behaviors have an evolutionary advantage or they would not have been retained for millions of years, chances are that this one too has helped us survive as a species. And, indeed, accumulating evidence strongly suggests that eating dirt is good for you.

    In studies of what is called the hygiene hypothesis, researchers are concluding that organisms like the millions of bacteria, viruses and especially worms that enter the body along with “dirt” spur the development of a healthy immune system. Several continuing studies suggest that worms may help to redirect an immune system that has gone awry and resulted in autoimmune disorders, allergies and asthma.

    These studies, along with epidemiological observations, seem to explain why immune system disorders like multiple sclerosis, Type 1 diabetes, inflammatory bowel disease, asthma and allergies have risen significantly in the United States and other developed countries.

    Training the Immune System

    “What a child is doing when he puts things in his mouth is allowing his immune response to explore his environment,” Mary Ruebush, a microbiology and immunology instructor, wrote in her new book, “Why Dirt Is Good” (Kaplan). “Not only does this allow for ‘practice’ of immune responses, which will be necessary for protection, but it also plays a critical role in teaching the immature immune response what is best ignored.”

    One leading researcher, Dr. Joel V. Weinstock, the director of gastroenterology and hepatology at Tufts Medical Center in Boston, said in an interview that the immune system at birth “is like an unprogrammed computer. It needs instruction.”

    He said that public health measures like cleaning up contaminated water and food have saved the lives of countless children, but they “also eliminated exposure to many organisms that are probably good for us.”

    “Children raised in an ultraclean environment,” he added, “are not being exposed to organisms that help them develop appropriate immune regulatory circuits.”

    Studies he 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.”

    Worms for Health

    In studies in mice, Dr. Weinstock and Dr. Elliott have used worms to both prevent and reverse autoimmune disease. Dr. Elliott said that in Argentina, researchers found that patients with multiple sclerosis who were infected with the human whipworm had milder cases and fewer flare-ups of their disease over a period of four and a half years. At the University of Wisconsin, Madison, Dr. John Fleming, a neurologist, is testing whether the pig whipworm can temper the effects of multiple sclerosis.

    In Gambia, the eradication of worms in some villages led to children’s having increased skin reactions to allergens, Dr. Elliott said. And pig whipworms, which reside only briefly in the human intestinal tract, have had “good effects” in treating the inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, he said.

    How may worms affect the immune system? Dr. Elliott explained that immune regulation is now known to be more complex than scientists thought when the hygiene hypothesis was first introduced by a British epidemiologist, David P. Strachan, in 1989. Dr. Strachan noted an association between large family size and reduced rates of asthma and allergies. Immunologists now recognize a four-point response system of helper T cells: Th 1, Th 2, Th 17 and regulatory T cells. Th 1 inhibits Th 2 and Th 17; Th 2 inhibits Th 1 and Th 17; and regulatory T cells inhibit all three, Dr. Elliott said.

    “A lot of inflammatory diseases — multiple sclerosis, Crohn’s disease, ulcerative colitis and asthma — are due to the activity of Th 17,” he explained. “If you infect mice with worms, Th 17 drops dramatically, and the activity of regulatory T cells is augmented.”

    In answer to the question, “Are we too clean?” Dr. Elliott said: “Dirtiness comes with a price. But cleanliness comes with a price, too. We’re not proposing a return to the germ-filled environment of the 1850s. But if we properly understand how organisms in the environment protect us, maybe we can give a vaccine or mimic their effects with some innocuous stimulus.”

    Wash in Moderation

    Dr. Ruebush, the “Why Dirt Is Good” author, does not suggest a return to filth, either. But she correctly points out that bacteria are everywhere: on us, in us and all around us. Most of these micro-organisms cause no problem, and many, like the ones that normally live in the digestive tract and produce life-sustaining nutrients, are essential to good health.

    “The typical human probably harbors some 90 trillion microbes,” she wrote. “The very fact that you have so many microbes of so many different kinds is what keeps you healthy most of the time.”

    Dr. Ruebush deplores the current fetish for the hundreds of antibacterial products that convey a false sense of security and may actually foster the development of antibiotic-resistant, disease-causing bacteria. Plain soap and water are all that are needed to become clean, she noted.

    “I certainly recommend washing your hands after using the bathroom, before eating, after changing a diaper, before and after handling food,” and whenever they’re visibly soiled, she wrote. When no running water is available and cleaning hands is essential, she suggests an alcohol-based hand sanitizer.

    Dr. Weinstock goes even further. “Children should be allowed to go barefoot in the dirt, play in the dirt, and not have to wash their hands when they come in to eat,” he said. He and Dr. Elliott pointed out that children who grow up on farms and are frequently exposed to worms and other organisms from farm animals are much less likely to develop allergies and autoimmune diseases.

    Also helpful, he said, is to “let kids have two dogs and a cat,” which will expose them to intestinal worms that can promote a healthy immune system.

    Source: The New York Times Copyright 2009 The New York Times Company (27/01/09)

    © Multiple Sclerosis Resource Centre (MSRC)

    How a parasite might hold clues for auto immune disease treatment

    Intestinal Worms

    Researchers at the Universities of Glasgow and Strathclyde will try to understand why auto immune diseases like rheumatoid arthritis and multiple sclerosis are so rare in countries where parasitic worm infections are common and whether this may lead to new effective arthritis treatments.

    Yes, that’s right. Parasitic worms living inside the bodies of populations from tropical regions without causing them any trouble at all. And perhaps, strangely, providing some benefit. Which leaves you to wonder if Mother Nature doesn’t know just exactly what she’s doing after all…

    The scientific community is well aware of an inverse relationship between worm infections and diseases like rheumatoid arthritis, inflammatory bowel disease, type-1 diabetes and multiple sclerosis. Countries where people are naturally infected with this particular parasite seem to have lower rates of these conditions than those countries where this type of infection doesn’t occur or has been eradicated.

    Luckily for the squeamish among us, it’s not the actual parasitic filarial nematode worm that the Scots scientists are wanting to put into our bodies, it’s a large molecule they secrete known as ES-62. This substance is found in the bloodstream of parasite infected people in the tropics, and seems to provide some protective benefit against the inflammation the worms should be causing in their human hosts. The good news is that ES-62 has no known adverse effects, leaving the body perfectly able to fight off other infections.

    “ES-62 appears to act like a ‘thermostat’ to effectively turn down disease-causing inflammation while leaving essential defense mechanisms intact to fight infection and cancer,” according to Iain McInnes, a member of the research team and Professor of Experimental Medicine at the University of Glasgow. “This property also makes ES-62 a unique tool for scientists to identifying how such disease-causing inflammation occurs.”

    The team is going to try and produce a synthetic version of the ES-62 molecule from the worms in an effort to come up with an anti inflammatory therapy that works effectively for auto immune diseases like rheumatoid arthritis, inflammatory bowel disease, type-1 diabetes and multiple sclerosis. The three-year study is being funded by the UK's Arthritis Research Campaign.

    Earlier work has also shown ES-62 to have real potential as a therapy for allergies too.

    Source: Artwoo ©2006-2008 ClknGo Software Corporation. (24/11/08)

    Parasitic infection is found to benefit MS patients

    Intestinal Worms

    Patients with multiple sclerosis who also happen to have an intestinal parasite appear to have significantly fewer relapses and better outcomes than other MS patients, a new study found.

    The finding suggests that when the body's immune system is occupied with an external threat, it might be less likely to misfire, which happens in conditions known as autoimmune disorders. Multiple sclerosis is an autoimmune disorder that attacks the myelin sheath that protects nerve fibres.

    The study tracked 12 multiple sclerosis patients who were found to have an intestinal parasite and compared them with 12 other patients. Over four years, there were stark differences. There were three relapses among the patients who had the intestinal infection and 56 relapses in the other group.

    Patients with the parasitic infection also had minimal changes in disability scores compared with the other group, according to a study in this month's Annals of Neurology by Jorge Correale and Mauricio Farez of the Raul Carrea Institute for Neurological Research in Buenos Aires.

    The study suggests that one reason for the apparent increase in autoimmune disorders in recent years could be the decline of infectious diseases in certain countries. Because parasites often cause long-lasting infections, the researchers hypothesised that such infections could make persistent demands on the body and thereby reduce the likelihood that the immune system will attack healthy tissue.

    Source: SouthCoastToday.com © 1995-2007 The Standard-Times.(16/05/07)

    Asphelia Announces Initiation of An Independent TSO Trial for Multiple Sclerosis

    Intestinal Worms

    As announced in the March 7th issue of the Wisconsin State Journal, Dr. John Fleming, a leading neurologist at the UW Hospital, is initiating an investigator-initiated IND clinical trial to assess the safety and efficacy of Trichuris suis ova (TSO) in the treatment of Multiple Sclerosis (MS). Dr. Fleming's trial is funded by the Multiple Sclerosis Society, and is the first of its kind within the United States.

    The concept of using TSO therapy to treat MS was sparked by evidence showing TSO boosts regulatory T cells, and may therefore be able to down-modulate pathways observed in Multiple Sclerosis (as well as in Crohn's Disease). Indeed, in a February 2007 publication in Annals of Neurology by Correale and Farez, et al. MS patients chronically populated with helminths experienced a significantly more favorable course of the disease, as compared with worm-free MS patients.

    Fleming's trial will launch in Wisconsin in April, and will focus on TSO's effects on the safety as well as the frequency and severity of clinical and radiographic exacerbations in patients with MS.

    About TSO: ASP1002 is a helminth ova (worm egg) technology currently being developed for the treatment of autoimmune diseases and immunological disorders, such as Crohn's Disease, Multiple Sclerosis, and asthma. More than 1,000 patients in Europe and the United States have taken TSO without significant side effects or safety issues.

    About Asphelia: Asphelia Pharmaceuticals is a privately-held, clinical-stage company focused on changing the course of immunological disorders. Asphelia's primary focus lies in its development of therapies targeting Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis), as well as other immunological and inflammatory disorders, including multiple sclerosis and asthma. Asphelia's lead compounds target the cause of Inflammatory Bowel Disease, not just its symptoms, in an effort to change the course of the diseases and allow patients new freedoms. Asphelia's immunotherapeutics seek to provide patients with safer, more effective and more convenient care.

    Source: Asphelia Pharmaceuticals (07/04/08)

    Can drinking worm eggs treat Multiple Sclerosis?

    Intestinal Worms

    Some UW Hospital patients will soon test an unusual treatment: They'll drink a cocktail of worm eggs, which will hatch inside their bodies.

    Doctors say the low-grade infection of worms, harvested from pigs, can help regulate faulty immune systems. The patients have multiple sclerosis, in which the immune system attacks nerve cells.

    "The yuck factor is hard to get over," acknowledged Dr. John Fleming, the UW Hospital neurologist who plans to launch a study of worm therapy next month. "But the idea has scientific merit."

    Patients with other conditions, such as irritable bowel syndrome, have tried worm therapy elsewhere. It has eased symptoms without causing known side effects.

    Many scientists believe the prevalence of such autoimmune conditions — including multiple sclerosis, allergies, asthma and a form of diabetes — is partly explained by a "hygiene hypothesis."

    Sanitary environments in developed countries have led to more of the diseases, the theory goes, because people's immune systems aren't properly trained by exposure to germs and parasites.

    The worm therapy offers a crash course of such training, Fleming said. "It stimulates the immune system in a good way."

    He said the concept is similar to eating yogurt, which contains helpful bacteria that regulate digestion.

    In the UW-Madison study, five patients with multiple sclerosis will sip a sports drink-like liquid every two weeks for three months. Each cup will contain 2,500 eggs of the whipworm, a tiny organism that commonly lives in humans and animals.

    Though the human whipworm rarely causes illness, the study uses a pig version that is benign in people, Fleming said.

    The eggs hatch into larvae, the size of an eyelash, that stick to the inside of the intestine. In killing the larvae, the body unleashes an extra dose of regulatory T cells, which dampen overactive immune cells.

    Existing multiple sclerosis treatments, all of them injections, also try to block overactive immune cells.

    But with the worm therapy, "instead of knocking down the bad parts of the immune system, we're pushing up the good parts," Fleming said.

    He is buying the egg-containing liquid from Ovamed, a German company that harvests the eggs from pigs.

    Multiple sclerosis can cause numbness, paralysis, blindness and other symptoms. Most patients have a "relapsing-remitting" form, in which flare-ups are followed by recovery periods.

    Fleming will check to see if the worm therapy reduces the frequency or severity of flare-ups. Patients will also undergo monthly MRI scans to see if fewer lesions develop in the brain and spinal cord, where the disease destroys nerve cells.

    If the study is successful, 15 patients will be enrolled in a follow-up trial for a year. Then a larger study might be launched comparing worm therapy with a placebo, or fake treatment.

    Worm therapy is a promising alternative treatment for the 400,000 Americans with multiple sclerosis, said Dr. John Richert. He is vice president for research and clinical programs at the National Multiple Sclerosis Society, which is funding Fleming's study.

    "We need to push for the development of new and safe medications," Richert said. "This is a direction that has a strong chance of bearing fruit."

    Fleming admits he was skeptical when he first heard of worm therapy. It was carried out a few years ago by Joel Weinstock of the University of Iowa, who is now at Tufts University in Boston.

    Zsuzsanna Fabry, a pathologist who worked with Weinstock in Iowa, is now at UW-Madison. She told Fleming of Weinstock's research, which had positive results in patients with irritable bowel syndrome.

    Fleming figured the same approach could work in multiple sclerosis.

    A study in Argentina backed up that hunch. It compared a dozen multiple sclerosis patients who were naturally infected with a similar worm with a dozen worm-free patients.

    Over four years, those with the worms had 90 percent fewer flare-ups and brain lesions.

    "This idea seems outrageous at first," Fleming said. "But many good, new ideas do."

    Source: madison.com © 2008 Capital Newspapers (07/03/08)

    © Multiple Sclerosis Resource Centre (MSRC) 

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