Multiple Sclerosis and Helminths: A Phase 2 Clinical Trial

I’m treating myself this week, writing about two of my favorite things:  first a post on “things you can do now,” and now a clinical trial, this one on using helminths to treat multiple sclerosis.[i]  This was a phase 2 study at the University of Nottingham in the UK using the helminth, human hookworm (Necator americanus), lasting a total of 9 months. Past studies (not double blind, placebo controlled, however) have shown tremendous success in using helminths to treat this illness.  I wrote an update on  this back in February.

For those unfamiliar, helminths (intestinal worms) are the main type of organism comprising the native macrobiome of all mammals.  They are potent stimulators of the immune’s regulatory system, which is the off-switch to the proinflammatory one.  We in the industrialized world have completely eradicated our macrobiomes, leading to an epidemic of chronic, systemic inflammation, and the diseases associated with that.  There are scores of articles on this topic on The Biome Buzz.  Here is a good starting place, if you’re interested in learning more.

In this trial, 71 patients were randomized to either a control group, or an experimental group which received 25 hookworm (HW). Only 66 ended up completing the trial for a variety of reasons but not because of adverse effects of the hookworm,  all of which were non- significant. MRI scans of their brains were performed monthly starting in month 3 through 3 months post-study.  The participants also had blood taken on regular intervals to measure inflammatory and regulatory (the off-switch to the inflammatory system) cytokines.

The results were interesting.  There was not a statistically significant difference at month 9 in the cumulative number of brain lesions (or newly enhanced lesions) between the two groups. However, 51% of the HW group, verses 28% of the placebo group, had no detectable MRI activity, which “…suggests a treatment effect.”  More than that, the trend in the treatment group was downward:  the researchers recognize in the paper that had the trial continued, the differences would have become statistically significant.  In fact, they state outright in their discussion that, “The treatment duration, 36 weeks, was relatively short.  Longer time (1-2 years) is needed to assess clinical response.”  I have mentioned this over and over and over again in my posts on the subject of helminths and trials:  the time of these trials is WAY too short to fairly judge efficacy – sometimes as short as 3 months!  Many papers in the literature note that it can take a year or more for full immune modulation by helminths to take effect.  So frustrating!

Another limitation of the study is that the researchers could not confirm active helminth infection in everyone in the experimental group.

The authors state that while they did not find a “…difference between the cumulative number of active MRI lesions in the 2 groups…the higher proportion of scans with no new activity in the HW group suggests a beneficial effect.”  Looking at the blood results, it was clear that “…HW have an anti-inflammatory immunobiological effect. Tregs were significantly increased compared with the placebo arm, in which it decreased.”

The conclusion:  this trial “…has shown the safety and tolerability of the treatment and a biological effect compatible with studies in which natural helminth infection has a protective effect in MS.  Infection with HW increased eosinophil counts and some Treg cell markers.”  So overall, a pretty successful phase 2 trial.

My final thought – a question that has me puzzled:  the trial was conducted between September 2012 and March 2016…and the study was published in June of this year.  Why did it take 4 years to get it published?!

__________________________________________________

[i] Tanasescu R, Tench CR, Constantinescu CS, et al. Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial. JAMA Neurol. Published online June 15, 2020. doi:10.1001/jamaneurol.2020.1118

Leave a Reply

%d bloggers like this: