Friday, November 30, 2012

All-Purpose Parasites: Why Parasites May Be The Next Miracle Drug

A long-term sufferer of Crohn’s disease makes yet another visit to his doctor, desperate to alleviate the symptoms he has been plagued by for so long. The patient has already undergone several surgeries to remove the portions of his intestine which were extensively damaged as a result of the disease, and can no longer work as the painful disease-related flare-ups have been increasing in frequency and intensity. The patient tells his doctor that he is desperate for relief and willing to try anything. After hearing this, the doctor considers the patient’s plea for a moment before handing him a prescription for parasites. The patient gratefully accepts the prescription and heads to the pharmacy, hoping that this will finally be the cure that he so badly needs.

Such a scene may seem unlikely, but it is already becoming a reality. The use of parasites in treating medical conditions at first seems counterintuitive, as they are primarily associated with their pathogenic qualities; however, a growing body of evidence indicates that parasite infection may be one of the most effective treatments for autoimmune diseases and allergies. For most people the idea of willingly infecting themselves with parasites may seem abhorrent, but for the millions of people who have suffered for years from painful and sometimes life-threatening autoimmune diseases and allergies, the choice is a no-brainer.

Our ancestors spent thousands of years evolving among a greater diversity of bacteria and parasites than we are accustomed to today. Parasite and bacterial infections were ubiquitous in Paleolithic times, and it wasn’t until the 1900s as industrialized urban cities began cropping up in developing countries that sanitation became a priority. Prior to improved sanitation, infectious diseases ravaged many communities and claimed thousands of lives. Most developed countries, therefore, tend to be intensely ‘germ-phobic’. The mere mention of bacteria and parasites makes most people shudder. In recent years, however, some of the stigma associated with certain bacteria and parasites has been reduced. It seems that being too clean has its own drawbacks, and now people in developed countries find themselves facing ailments which were unheard of prior to industrialization.

It is only within the past century that the incidence of allergies and autoimmune diseases has begun skyrocketing, an increase which is seen almost exclusively in developed or developing countries. Wealthy, industrialized countries have lower rates of parasite infection and yet have significantly higher rates of autoimmune diseases and allergies. While genetics seems to play a role in the development of these conditions, it does not adequately explain the disproportionate increase in autoimmune disease and allergies.

It has been demonstrated that environment also has a significant impact on our immune systems. Compared to most developing countries, industrialized countries are much ‘cleaner’- sanitation is more stringent, the citizens tend to be more informed about good hygiene, and the threat of infectious disease- including parasites- is minimal. Scientists are beginning to question, however, whether there is such a thing as being too clean.

In almost all developing or third-world countries, allergies and autoimmune diseases are practically nonexistent. Autoimmune diseases such as Type 1 Diabetes and Multiple Sclerosis, rare in African and certain Asian populations, increase when these populations migrate to a more industrialized environment, according to data from the World Health Organization (WHO). This effect is underlined by research conducted using mice as a model for Type 1 Diabetes. Non-Obese Diabetic (NOD) mice spontaneously develop symptoms mimicking Type 1 Diabetes in humans. Researchers have demonstrated that the onset and frequency of Type 1 Diabetes in NOD mice increased in mice raised in a controlled and sterile environment, while onset of diabetes symptoms is prevented in mice infected with parasites or a virus which affects the immune system in a similar manner.

While Type 1 Diabetes is only one example of an autoimmune disease which has become prevalent in modern society, similar effects have been observed in a surprising number of different diseases related to a malfunctioning immune system. Proponents of parasite therapy contend that the inverse correlation between parasite infections and the incidence of autoimmune diseases and allergies is in part explained by the ‘hygiene hypothesis’- in short, people in the United States and other highly developed countries are simply too clean, and haven’t had enough exposure to ‘germs’ and parasites. The foundation for the hygiene hypothesis was laid out by David Strachan in a 1989 paper published in the British Medical Journal on an epidemiological study of hay fever among British children that he had conducted for a length of 23 years. In the conclusion of the paper Strachan wrote of his observations that “allergic diseases [could be] prevented by infection in early childhood” and that “later infection or reinfection…might confer additional protection against hay fever”.

            Part of the ‘hygiene hypothesis’ maintains that throughout evolution, the immune system has been primed to remain at a baseline level of activity in response to a constant assault by bacteria, parasites, and viruses. Our immune systems, moreover, have evolved to become accustomed to infection by parasites and other invaders. In the absence of the appropriate immune challenges and itching for a fight, our immune systems begin attacking harmless substances (dust, peanuts, soybeans), or even our own bodies.

Ideally, our immune systems should function like a well-trained army: when a threat is perceived, the soldiers are given their instructions and advance an elegantly orchestrated attack against the invader. After the battle has been won, the soldiers- white blood cells and other immune system mediators- cease fighting, return to their barracks, and peace is restored. In autoimmune diseases and allergies, however, the soldiers ignore the cue to stop fighting, and initiate attack even in the absence of a threat. Normally the soldiers are trained to differentiate between the ‘enemy’ and their own forces; in autoimmune diseases, however, our bodies are assaulted by friendly fire from our own immune systems.

Parasites are one such target of the immune system. For thousands of years, however, parasites have been a part of the lives of modern humans- literally- and so the ‘Old Friends’ hypothesis refines the hygiene hypothesis through an added caveat. According to the old friends hypothesis, humans evolved alongside particularly abundant but harmless bacteria and parasites, and so our immune systems were trained to ignore otherwise harmless invaders because there were simply so many. Fighting off non-threatening microorganisms was a waste of time, energy, and resources for our immune systems.

Just like many young children sent off to school quickly learn to socialize and ‘play nice’ with their peers, the old friends hypothesis claims that our immune systems have also learned to be tolerant of certain microorganisms. Young children quickly learn that if you ignore the taunts of the playground bully, their antagonizer is often rendered harmless; after frequent invasion by certain abundant bacteria or large parasites our immune systems also learned that it just wasn’t worth the time and energy to fight off the invaders as long as they weren’t creating too much trouble within our bodies. As strange as it sounds, parasite and bacterial infections may be necessary for the proper development of our immune systems. Without the proper ‘training’ early on, our immune systems are not learning how to regulate themselves properly.

In the same way that humans have evolved and adapted to frequent invasion by parasites, parasites have also adapted to live with humans. Many parasites manage to avoid the threat of immune attack when colonizing humans because they have developed the means to evade the surveillance of the immune system and attenuate the immune response so that they can live and reproduce in peace within their host organism. This is primarily accomplished in two ways: first, parasites activate the regulatory T cells which normally keep the immune system in check. When regulatory T cells are activated, they prevent the immune system from mounting an immune response. Next, parasites act on the cells which normally initiate the inflammatory response to foreign objects. The use of parasites for therapeutic purposes exploits these qualities: not only do the parasites minimize the activity of the immune system, but when detected most of the immune system’s resources are directed towards fighting off the invading parasites, relieving the immune system’s attack on the body’s own tissues and organs.

In a recent article published in the journal Nature, Joel Weinstock, a pioneer of helminth therapy, refers to the evolutionary dynamic between parasites and their human hosts as being essential to shaping our immune systems and explains that “the evil properties of intestinal parasites are often overblown…. clearly, after thousands of years of co-evolution, the human immune system has evolved to handle the presence of most parasitic worms, which have, in turn, developed adaptations that enable them to live for years in a human host”.

In the article, Weinstock describes a flight to a grant-review session at the Crohn’s and Colitis Foundation of America as being a pivotal moment in his scientific career. At that point he was familiar with the hygiene hypothesis, and had previously conducted research on parasites. He also knew that parasite infection rates tended to inversely correlate with the incidence of autoimmune diseases in certain populations. When Weinstock first began speculating that parasites may have a therapeutic effect on patients with autoimmune diseases, he conducted preliminary research using mice with symptoms mimicking inflammatory bowel disease in humans. Administering parasites to the afflicted mice, he found, protected them from the disease, as he had predicted. Weinstock and his team were subsequently granted approval to test the parasite therapy in a single Crohn’s patient. The patient’s symptoms improved for several months after being given parasite eggs, without any adverse side effects. When the pilot study was declared successful, the medical testing eventually expanded to include 29 additional Crohn’s patients. The trial was an overwhelming success- nearly 80% of the Crohn’s patients exhibited a significant decrease in the severity of their symptoms, and 72% of the patients tested went into remission, with no reported side effects. Similar positive results were seen in a trial of 54 patients with ulcerative colitis, with almost 43% showing significant improvement.

The efficacy of parasite therapy is not limited to autoimmune inflammatory bowel diseases, however. Parasite therapy shows promise in treating a wide range of inflammatory disorders. A growing faction of scientists and medical practitioners now believe that in some autistic patients chronic inflammation may be to blame for their symptoms. Several studies have reported finding evidence of increased active inflammation and inflammatory signaling molecules in the brains of autistic patients and the fluid surrounding the brain and spinal cord. Following the same logic as the use of parasites in treating autoimmune disorders and allergies, clinical trials using pig parasitic whipworms to treat adults with autism are already underway. The trials are preceded by one case in which the father of an autistic child started his child on a parasite therapy regimen which essentially reversed the child’s symptoms, including the disruptive behavior which was beginning to spiral out of control prior to the parasite treatment.

Parasite therapy has been steadily gaining credibility among scientists and medical professionals, and now it is also getting the attention of pharmaceutical and biotech companies. Coronado Biosciences, a US Biotech company, began clinical trials for their newest ‘drug’, TSO (Trichuris suis ova), in August. A dose of TSO is no more than pig whipworm eggs in saline solution, to be taken every two weeks or as often as patients are advised to do so by their doctors. A similar trial is being conducted simultaneously in Europe by Coronado’s German collaborators at Dr. Falk Pharma GmbH. Pig whipworms, a type of helminth, are the only parasites which have been approved for use in clinical trials and medical research in the United States. The human gut is a dead end for mature pig whipworms, therefore the risk of re-infection or transmission to other people is minimal. The helminthes are unable to reproduce in humans, and so after the whipworm eggs are swallowed they hatch and briefly colonize the intestine before dying off two months later. Like most drugs, the helminth egg capsules need to be taken repeatedly to maintain the benefits of the therapy and keep patients’ symptoms at bay.

Gaining approval for parasite treatment as a standardized medical therapy, however, is most likely a long way off. The clinical trials which are currently being conducted were put off for years pending approval, and they are only officially recognized as ‘safety’ trials to determine whether there any negative consequences of pig whipworm ingestion. The results seem promising, and to date no complications or side effects as a result of treatment with pig whipworms have been reported.

If the results of the current and upcoming clinical trials continue to be as positive as in previous studies, it will be only a matter of time before pharmacies routinely stock their shelves with parasite eggs. Now that their reputation has been getting a makeover in the medical community, parasites, the scourge of public health officials and epidemiologists, may turn out to be a blessing for the millions of people suffering from severe, life-threatening allergies and autoimmune diseases.

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