There have been several small studies looking at whether deliberately exposing people with multiple sclerosis to parasitic worms (helminths) can reduce their levels of inflammation and reduce their MS disease activity.
This research arose after it was observed that some conditions, including MS, are less prevalent in countries where parasitic worm infections are common. This gave rise to the 'hygiene hypothesis' or the 'old friends' theory' that a cleaner modern lifestyle means that children are no longer exposed to infections, parasites and other environmental factors to the same degree as previously, and that this has led to an increase in susceptibility to conditions such as asthma, inflammatory bowel disease and MS.
The first evidence that infection with parasitic worms may be beneficial in MS came from a study in 2007. This followed 12 people with relapsing remitting MS who had naturally become infected with a parasitic worm and compared them with 12 patients who weren't infected. Participants were followed for an average of four and a half years. In this time, there were three clinical relapses in the infected group, compared with 56 in the uninfected group. 11 of the uninfected group showed an increase in their EDSS score during the study, compared to two of the infected group.
The group were followed for a further five to seven years. Several of the infected patients went on to develop severe gastrointestinal problems and so were treated to clear the parasites. Elimination of the parasites led to an increase in those people's MS disease activity to a similar level to those who were never infected. These findings supported the theory that infecting people with parasitic worms might be a feasible approach for treating MS, and led to several further small trials, some of which are detailed below.
There are several different types of parasitic worms such as flatworms (including flukes), roundworms (including whipworms and hookworms) and tapeworms. Most research in MS has looked at whipworms and hookworms. Results from the trials have been mixed.
Several small phase I studies have looked at the oral administration of the eggs (ova) of the pig whipworm Trichuris suis. The whipworm is a type of parasitic roundworm that hatches in the small intestine before moving as adults to the large intestine. Research has also looked at using whipworms to treat conditions including Crohn's disease, ulcerative colitis and autism.
In 2011, the HINT 1 trial treated five people with relapsing remitting MS by administering 2,500 pig whipworm ova every two weeks for three months. It found the treatment was safe and favourable trends were seen on MRI scans and in measures of cells in the immune system.
In the same year a trial by a differnet group (TRIMS-A) involved 10 people with relapsing remitting MS. Like the HINT 1 trial, the participants were dosed with 2,500 pig whipworm ova every two weeks for three months. Again the treatment was found to be well tolerated, although some participants experienced some gastrointestinal symptoms such as mild abdominal pain, flatulence or, in one case, diarrhoea. However, in this study no beneficial effect was seen on the course of MS.
A more recent trial (HINT 2) reported its results in 2017. The trial involved 16 people with relapsing remitting MS. They were generally young, hadn't had MS for very long and had mild levels of disability. In this study, the participants were treated with 2,500 pig whipworm eggs every two weeks for 10 months. Like the other trials, the treatment was well tolerated with the exception of some mild gastrointestinal symptoms. Although treatment generally had a favourable effect on MRI measures, for example a reduction in the number of active lesions seen, the size of these effects were modest and there was a lot of variation between individual responses.
A UK study based at the University of Nottingham (WIRMS trial) has looked at the effects of hookworms on MS. The hookworm is a roundworm that lives in the small intestine of its host. Hookworm larvae are found in soil contaminated by human faeces, most infections occur in countries such as Africa, the Americas, China and South East Asia. The larvae can infect people by penetrating their skin if it comes into contact with the soil - for example if walking barefoot. Hookworm infection has been found to have beneficial effects on people with conditions linked to overactive immune systems, including asthma and Crohn's disease.
The researchers suggested that infection with hookworms could cause a decrease in the normal inflammation associated with MS and less MS disease activity. To test this theory, the WIRMS trial (Worms for Immune Regulation of Multiple Sclerosis) recruited 72 patients with relapsing remitting MS. Half were randomised to receive 25 Necator americanus (hookworm) larvae whilst the other half received a placebo.
The hookworm larvae were administered through the skin by pipetting a solution of the larvae onto a plaster dressing which was placed on the upper arm for 24 hours. Once the larvae come into contact with the skin, they burrow through and work their way into the bloodstream. Their final destination is the gut, where they latch on to the lining of the small intestine. The placebo was pharmaceutical grade water pipetted onto the plaster.
Participants were given regular blood tests to ensure they weren't anaemic, which would indicate that the dose of 25 larvae was too high - if this was the case the worms were eradicated. At the start of the trial the participants underwent a baseline MRI scan. They were then scanned at regular intervals for nine months to look for new or worsening lesions. At month nine they were given a medication to eradicate the worms and then a final MRI scan was performed at month 12.
The results, published in 2020, showed that although there was some indication of an effect, people infected with hookworms did not do significantly better than a placebo group.
A study published in 2021 looked for the first time to see what effect treatment with the hookworm Necator americanus had on the composition of the bacteria in the faeces of a group of people with relapsing MS. The trial found that those participants in the trial who were infected with the hookworm had a more diverse range of bacteria in their faeces than the control group. This increase in bacterial diversity was especially seen in the treated individuals who experienced no relapses (clinical or radiological) during the trial. The researchers concluded that this study lends support to the theory that the changes in the composition of the microbes found in the gut associated with the hookworms, contributes to their immune modulating properties.
The use of live parasitic worms is not thought to be the optimal way to treat people and has yielded mixed results in trials which haven't fully supported the initial observations in the group who were infected naturally. Not only do patients have a negative attitude to being infected with live parasites, there is also the possibility of adverse side effects following infection. Some may be relatively mild, such as gastrointestinal side effects, but more seriously in some people there is the potential for their condition to be made worse.
This has led researchers to look at alternatives. One approach is to try and identify the specific molecules that the parasitic worms are producing that can modulate the immune system. These could then be synthesised in the laboratoy and provide a safer option for treatment.
In 2014, Australian researchers identified a molecule called AcK1 in parasitic worms that reduces immune activity. Another group in Australia have identified a molecule called FhHDM-1, which is secreted by the liver fluke Fasciola hepatica, which has been shown to be a potent immune modulator and the group have seen positive results in a mouse model of MS with this molecule.
This type of work may eventually lead to treatments for autoimmune conditions such as MS that don't require ingesting actual worms.
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- BMC Biology 2021;19(1):74. Full article Experimental infection with the hookworm, Necator americanus, is associated with stable gut microbiota diversity in human volunteers with relapsing multiple sclerosis.