Researchers across the board are keen to discourage self-infection, which they say puts patients at risk of taking the wrong dose or purchasing contaminated batches. Fleming says he advises the multiple sclerosis patients who email him at a rate of around one a week against self-infecting with helminths. “People might say they’re getting better or worse, but they don’t really know,” he says. “Outside a scientific trial, it’s a muddle.”
Nowadays, most researchers investigating helminthic therapies have abandoned blood-sucking hookworms in favour of pig whipworms, as they have evolved to colonise swine and therefore cannot complete their life cycle within humans. Patients must re-infect themselves every few weeks but do not risk a chronic infection potentially spiralling out of control, or of accidentally infecting family members. “Pig whipworm is very kosher,” Weinstock says.
At New York University, immunologist P’ng Loke found monkeys suffering from chronic diarrhoea not only got better after receiving a dose of pig whipworms but also had significantly different gut microbes post-infection. He is currently enrolling ulcerative colitis patients to repeat the experiment in humans.
Gastroenterologist John Croese, at the Prince Charles Hospital in Brisbane, is inoculating 12 coeliac disease patients, who suffer from gluten intolerance, with hookworms. Gluten is slowly introduced into their diets to see if the hookworms will suppress the disease’s inflammatory response.
Back in Wisconsin, Fleming is continuing his studies on multiple sclerosis. He has enrolled another 15 patients for a longer trial with pig whipworms, the results of which are expected at the end of this year. As for Weinstock and Elliott, they have returned to mouse models, seeking to understand how helminths inhibit disease.
Coronado Biosciences, a Massachusetts-based company, hopes to have results from two large studies being carried out in the US into the use of pig whipworm eggs to treat Crohn’s disease by the end of the year. Meanwhile, German firm Dr Falk Pharma is collaborating with Coronado in a similar trial.
Coronado also expects results from its multiple sclerosis trials next year. Trials on adults with autism are underway, and the firm is planning studies on psoriasis, ulcerative colitis, type 1 diabetes and children with autism. “Our most important task now is to identify which diseases to pursue and which patient populations to target," says Karin Hehenberger, Coronado’s chief medical officer.
None of these trials have reached phase 3, the final testing stage required to gain approval. Even if they are successful it is likely to be a few more years before treatments are made available to patients. Frustrating though it may be for some, developing new modes of therapies simply takes a long time. Gaining approval for trials, recruiting patients and waiting to evaluate the effects are all time-consuming.
It’s not just a case of demonstrating helminthic therapy is safe and effective, researchers will also have to figure out how to administer it. A live organism’s many complex molecular interactions with its host may be key to triggering the desired immune-suppressing reaction. It may therefore make sense to administer helminths as "living probiotics". In the case of whipworms this means patients swallowing doses of live eggs; in the case of hookworms they apply gauzes containing live larvae to their skin. “When you give someone a live worm, it’s like giving them the factory that makes the products and letting the factory do what it needs to do,” Elliott says. “Evolution has already created this thing.”
Others oppose this approach. “These worms are not benign," says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. "We can design better, bona fide treatments based on the biology of the worms that can be scaled up and manufactured without the complexities or safety issues that go along with administering live parasites."