Today I get to write about something other than the bacterial microbiome! Woopa! I was very happy to find a new paper on the possibilities of using helminths (helminth immunotherapy (HIT), as these authors call it) to prevent and alleviate multiple sclerosis (MS).[i] The article gives a great overall picture of where we currently stand, research- wise, and what work needs to be done going forward. More than that, I also learned some new tidbits which I think are very worth sharing with you.
I’ve written before about helminths and MS. As these authors acknowledge, what we currently know holds great hope, although it is a fraction of what we need to know. Still, the majority of the current studies (20 of 23), “…reported a protective effect of HIT…especially when the helminth or helminth-derived product was provided prophylactically…” Few studies currently exist on using HIT for those already affected – but I’ll come back to that in a moment as those studies too, hold promise.
One of the main issues in the field is lack of “technical” consistency. The existing studies have used many different species of helminth and those organisms were used in many different ways. In spite of this though, there is an overall remarkable consistency in findings. For example, there is great consistency in all these varied experiments in the way the immune system responds to the presence of helminths: they stimulate the Th2 family of cytokines, which includes regulatory ones, leading to lower levels of inflammation. Another interesting, and consistent, finding has to do with the B cells of the immune system. Generally speaking, depleting these kinds of immune cells via pharmaceutical works well for ameliorating the symptoms of MS, and thus are considered “major players in MS pathogenesis.”
Very little work (2 studies so far) has been done looking at helminths’ effects on B cells, but what we do know is that when an organism has helminths, B cells are implicated in promoting the Th2 response. In one study, the researchers transferred B cells from helminth-infected mice with the MS-like syndrome into mice who were also afflicted, but who did not have helminths. These B cells diminished the MS-like symptoms in the latter mice. In a human study, B cells from helminth-infected MS patients were shown to suppress inflammatory cytokine production and to stimulate regulatory cytokines: “Altogether, these observations suggest that HIT may modulate B cell function and contribute to the beneficial outcomes in…MS.”
Of the studies done thus far (in animal models, in which an MS-like syndrome is induced), only two have shown no protective effect from helminths. However, results of these must be interpreted with caution. In one of them, the helminths were cleared before MS was induced, “…which could explain the lack of an effect.” In the other, a helminth-derived product was used – not a living organism. The paper states that “…the majority of animal studies support the hypothesis that pre-existing helminth infection can limit the onset of MS-like symptoms in experimental models.”
The article points out that most people turn to helminths after diagnosis, and thus, studies looking at the effects helminths may have on alleviating symptoms are particularly useful. Unfortunately, there are very few of these. One unsuccessful one again used a product derived from Schistosoma eggs, not the actual organism. Products derived from other helminths were more successful. In one study, using the actual organism H. Polygyrus, partial remission was noted at only 3 weeks post inoculation. The best human study, covering a period of 5 years, I have discussed before in that earlier post. Those with MS who had helminths fared way better than those without, with no worsening of symptoms or new brain lesions.
Thus far, there have been 4 human clinical trials which have reported results. They all used Trichuris suis ova, TSO (which is a porcine-native whipworm), and varied greatly in length, from 3 to 10 months. The only one which saw no improving trends was the 3 months one. It appears, based upon these studies, that the longer the patient has had helminths, they better they continue to do (i.e. an uphill trend).
I feel like a broken record writing this, but we may as well get used to it because there is always more to be learned. In this case, we really, really need more science before we know how to best to dose helminths, which ones are the best organisms (which will likely vary from disease to disease), and so forth. Still, as this paper concludes, “…although there are only a limited number of studies that have tested whether HIT can have therapeutic effects once disease is established, there are indication of beneficial effect using some HIT regimes…”
[i] Charabati, M, Donkers, SJ, Kirkland, MC, Osborne, LC. A critical analysis of helminth immunotherapy in multiple sclerosis. Multiple Sclerosis Journal. 2020. doi: 10.1177/1352458519899040