Hookworm treatment shows ‘modest’ potential for recurring MS
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Controlled hookworm infection in patients with recurring multiple sclerosis is safe and showed potential to provide therapeutic benefits, according to a study published in JAMA Neurology.
“There is epidemiological evidence that in developing countries with high prevalence of natural infection with intestinal parasites, the prevalence of some inflammatory diseases, including MS, is low,” Cris S. Constantinescu, MD, PhD, FRCP, professor of neurology at the University of Nottingham, United Kingdom, told Healio Primary Care.
Constantinescu worked with David Pritchard, PhD, an immunoparasitologist and a professor of parasite immunology at the University of Nottingham who has pioneered studies of controlled hookworm infection, to develop the study after evidence emerged from Argentina that suggested patients with MS who were naturally infected with parasites had a milder MS disease course.
The study was a double-blind, randomized, placebo-controlled trial that included patients aged 18 to 61 years with relapsing MS who were recruited from a single tertiary referral center.
Once enrolled, patients were randomly assigned to placebo or experimental infection with 25 Necator americanus larvae, which were pipetted on a pad of gauze and placed on the patients’ arm for more than 30 minutes.
The researchers called participants at 1 week for a wellness check, and participants presented for visits at every month for 10 months and again at month 12. MRIs were conducted monthly from months 3 to 9, and again 3 months after the end of treatment. The researchers also assessed blood cell counts, stool samples and urine pregnancy tests during routine visits.
A total of 71 patients were randomly assigned to hookworm or placebo, and 66 patients completed the trial.
Constantinescu and colleagues determined that the median cumulative number of new, enlarging or enhanced lesions were not significantly different between the treatment groups.
More patients in the hookworm group (18 patients; 51%) than the placebo group (10 patients; 28%) had no detectable MRI activity, according to the researchers.
They found that the percentage of CD4+CD25highCD 127neg T cells increased in the hookworm group at month 9 (hookworm = 32 [4.4%]; placebo = 34 [3.9%]; P = .01).
None of the study participants withdrew due to adverse events, and researchers reported that aside from more application-site skin discomfort in the hookworm group (82%) than the placebo group (28%), there were no differences in adverse events.
Among participants, five relapses occurred in the hookworm group and 11 occurred in the placebo group during the study.
“Clinically, the study showed a modest therapeutic effect in MS,” Constantinescu said. “This means that this approach can be successful. However, as there are a number of very potent disease-modifying treatments in MS today, the appropriate people — possibly with milder or earlier disease — need to be selected. Also, strategies to enhance the immunomodulatory and therapeutic effect need to be found.”
He said hookworm infection treatment is not widely available in the United States, but there have been trials done using whipworm (Trichuris suis ova) in recurring MS in the country. However, he noted that the present study is larger, placebo-controlled and that hookworm only requires one-off treatment, while whipworm requires oral ingestion of eggs every 2 weeks.
In an editorial accompanying the study, Daniel Ontaneda, MD, PhD, and Jeffrey A. Cohen, MD, both of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic’s Neurological Institute, wrote that the treatment appears safe, but “its efficacy appears modest, making it unlikely to be a sufficient stand-alone treatment for MS.”
The use of this and similar parasitic worm infections as an “add-on treatment is difficult given the potential increase in infection rates when used with concomitant immunomodulating medications, particularly N. americanus, a known human pathogen (in contrast to [Trichuris suis ova]),” they wrote.
References:
- Ontaneda D, et al. JAMA Neurol. 2020;doi:10.1001/jamaneurol.2020.0519.
- Tanasescu R, et al. JAMA Neurol. 2020;doi:10.1001/jamaneurol.2020.1118.