From extending lifespan to bolstering the immune system, the drug’s effects are only just beginning to be understood.
Autism researchers are testing the ability of whipworm eggs to treat autism in a new clinical trial.
November 27, 2012|
Wikipedia, Universidad de Córdoba.A growing body of evidence suggests that in some patients, increased inflammation contributes to autistic behaviors. Now, a Phase I clinical trial is under way to measure the effects of infecting autistic patients with a non-pathogenic parasitic worm. Scientists at Montefiore Medical Center at the Albert Einstein College of Medicine in New York and biotech company Coronado Biosciences will test the hypothesis that treating these patients with Trichuris suis, a non-pathogenic parasitic pig whipworm, will dampen their immune responses and ameliorate repetitive and irritable behaviors.
“The trial is a novel approach [to autism treatment] with a naturally occurring drug delivery system”—a parasitic worm, said Eric Hollander, a Montefiore psychiatrist and head scientist on the trial.
Autoimmune and allergic diseases are more prevalent in more developed countries where citizens are accustomed to better water quality and less contact with farm animals. Some researchers chalk this phenomenon up to the so-called hygiene hypothesis, which posits that the microbes and parasites that humans co-evolved with act to help keep our immune responses in check. The theory was spurred initially by observations in humans—that after anti-parasitic therapy, people scored higher on allergy skin prick tests, or that autoimmunity and allergies were more prevalent in more-developed West Germany than East Germany—and supported by laboratory studies on mouse models of such diseases, said Marie-Helen Jouvin, a pathologist at Beth Israel Deaconess Medical Center and Harvard University, who is not involved in the clinical trial. Parasites, such as the whipworm used in the autism trial, are thought to both dampen inflammation and stimulate immune regulatory pathways in their hosts.
The idea to tackle autism symptoms with parasitic worms came from Stewart Johnson, the father of an autistic boy, who learned of the hygiene hypothesis while researching tantalizing links between autism and immunity. (Read more in The Scientist’s feature “Opening a Can of Worms.”) Stewart dosed his teenage son—under Hollander’s supervision—with eggs from the helminth Trichuris suis, which infects and is harmful to pigs but is not pathogenic in humans. With continued treatment, repetitive behaviors, resistance to change, and irritability all decreased in Stewart’s son, said Hollander.
“There are a number of epidemiological studies showing that there’s an increase in autoimmunity in families with autism,” said Paul Patterson, a neurobiologist at the California Institute of Technology who is not associated with the trial. “So therapies that modulate the immune system seem like a logical possibility.”
In addition to physical symptoms, a disordered immune response can produce neurological symptoms as well, noted Judy Van de Water, an immunologist at the University of California, Davis, who is a scientific consultant for Coronado Biosciences on autoimmunity and autism. Schizophrenia and autism are two disorders linked to aberrant inflammatory responses. Some cases of autism are associated with symptoms such as increases in inflammatory cytokines in the patient’s blood and anti-brain autoantibodies. Additionally, in animal models, aberrant maternal inflammation during gestation is also correlated with autistic behaviors and long-term immune system effects, suggesting that a mother’s immune response can “imprint” how her child’s immune system responds to activation later, said Van de Water. She cautions, however, that not all autistic individuals display characteristics of chronic inflammation—some actually have immune deficits, making it important to tailor any therapy to an individual.
Stewart’s success prompted Hollander to initiate a more rigorous trial of Trichuris suis ova (TSO) in treating autistic behaviors. Supported by Simons Autism Research Initiative and using TSO supplied by Coronado Biosciences, Hollander will give TSO to 10 young autistic adults between the ages of 18 and 35 in a double-blind controlled trial. TSO, which has been demonstrated safe in trials of ulcerative colitis, doesn’t penetrate the gut of humans, so there’s little risk of chronic infection. The study group will be divided into two—one will receive regular doses of TSO for 12 weeks while the other group receives a placebo. Then, after a two-week “washout” period (when the worms will pass from the patients’ intestines), the groups will switch treatments.
This crossover design helps increase the statistical power of the study, despite the small cohort, explained Bobby Sandage, Coronado’s CEO. Patients will be evaluated on various measures of autism symptoms, including repetitive behaviors, obsessive-compulsive behaviors, and aggression. Coronado is also testing TSO against a variety of classic autoimmune disorders, including multiple sclerosis and Crohn’s disease. The treatment has shown a strong safety record, even when taken by inflammatory bowel disease patients on immunosuppressants, noted Jouvin. Hollander and Sandage said that they hope to have results within a year.
As promising as TSO may be, Patterson counsels caution. “I think [TSO] is a blunt instrument,” he said. “We don’t know how it works, and it may have lots of different effects, probably not all positive.” Even if TSO therapy does not pan out, it may point the way to other treatments. A large percentage of autistic individuals also have gastrointestinal disorders, and TSO was recently shown to affect the microbial ecosystem of rhesus macaques. Patterson’s own work suggests that probiotic therapy can alleviate some autistic symptoms in a mouse model of autism.
November 28, 2012
Is it possible that the young man's behavior improved because of the extra attention he would have received in preparation for and administration of the treatment?
November 28, 2012
One of the health challenges in developed countries is the level of allergies and related (asthma, etc) conditions. It has also been reported that in countries with a higher level of exposure to parasites, there is a significant decrease in these conditions. So, could it be beneficial, with young children (infants) with families prone to severe allergies and asthma, to be inocculated with this or a similar non-pathogenic parasite? This would seem to be a relatively safe, and straight-forward study which could have significant ramifications if fruitful.
November 28, 2012
The experiment seems to follow more ideological guidelines than scientific ones. It reminds me of the bloodletting treatments of antiquity that were pseudo-supported by the "theory of humors." I think it is dangerous and, as much of today's psychiatric inquiries, a positive result with an n=1 is considered encouraging. Moreover, it is highly possible that, as "csoehl" (posting above) reminds us, there is a possiblity that this is a "Clever Hans Effect." Kluge Hans was the "clever" Berliner horse of astonishing cognitive abilities: he could answer mathematical questions of medium complexity (OK! he was a horse, after all) that were posed to him orally and in written form and he answered by tapping with his hoofs. Around 1910 Hans behavior was studied by the psychologist Pfungst, and he found that Hans was actually responding to the cues (body language) provided by his owner without the owner being aware that he was providing such cues. There was no "trick" or dishonesty, just need to believe. Today we call this an "observer-expectancy effect." A good effect in eliciting, or increasing, social participation and emotional responses in autistic children can be obtained with the use of an iPad and apps downloaded from the site Autism Speaks. The effect is not a cure and is not sustained after the iPad is taken away, but at least they do not make the kids ingest potentially dangerous sow parasites, and might be better, if not as good. Now... tap once for "yes" and two for "no".
November 28, 2012
I don't believe so. I read an article (elsewhere) about that father who searched for years for some kind of therapy to help his autistic son. It is inconceiveable that the level of attention given to his son was any different during the worm treatment than all the other therapies previously tried by the frustrated parents.
November 29, 2012
This story was presented broadly in 08.11.12 issue of NATURE, in Comments section. Extremely interesting, considering the overall increase in autoimmune diseases in high hygiene standards countries. But perhaps instead of increasing the infection with parasites we should concentrate on increasing the biodiversity and health of our intestinal flora? There are reports where use of intestinal flora from healthy donors helped patients with Crohn`s as well...
I agree with jtrott, this is not an extra attention effect, the parents who would try such therapy must have already gone through a lot - as a matter of fact the article was published here, https://www.the-scientist.com/?articles.view/articleNo/30802/title/Opening-a-Can-of-Worms/. I think, it is really great that it has moved to clinical trials since then.
November 29, 2012
You might wish to read Emily Willingham's detailed (and highly skeptical) analysis of theory: http://www.emilywillinghamphd.com/2012/08/autism-immunity-inflammation-and-new.html
(Willingham is a scientist, science editor, and mother of a child with autism.)
December 1, 2012
A future double blind study would nicely rule out whether extra attention is the cause for improvement
I hope this pans out. And I hope the tinfoil hat brigade denounces this as misinformaiton
December 1, 2012
typo, it should be "tinfoil hat brigade does not denounce"
December 17, 2012
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