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Original Investigation
June 15, 2020

Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial

Author Affiliations
  • 1Division of Clinical Neuroscience, University of Nottingham, Nottingham, England
  • 2Department of Neurology, Nottingham University Hospitals National Health Service Trust, Nottingham, England
  • 3Division of Clinical Neurosciences, University of Medicine and Pharmacy Carol Davila Bucharest, Bucharest, Romania
  • 4Department of Neurology, Colentina Hospital, Bucharest, Romania
  • 5National Institute of Health Research Nottingham BRC, Nottingham, England
  • 6Immune Regulation Research Group, University of Nottingham, Nottingham, England
  • 7Flow Cytometry Facilities, School of Life Sciences, University of Nottingham, Nottingham, England
  • 8Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, England
  • 9Department of Veterinary Medicine, University of Cambridge, Cambridge, England
JAMA Neurol. Published online June 15, 2020. doi:10.1001/jamaneurol.2020.1118
Key Points

Question  What are the effects of hookworm treatment compared with placebo on relapsing multiple sclerosis?

Findings  In this randomized clinical trial that included 71 patients, the median cumulative numbers of new magnetic resonance imaging lesions were not significantly different between the groups, but approximately half of participants treated with hookworm vs approximately a quarter of those receiving placebo had no detectable magnetic resonance activity. Hookworm significantly increased T regulatory cell counts in peripheral blood.

Meaning  The data from this study suggest a possible, albeit mild, therapeutic effect of hookworm infection in relapsing multiple sclerosis that warrants further study.


Importance  Studies suggest gut worms induce immune responses that can protect against multiple sclerosis (MS). To our knowledge, there are no controlled treatment trials with helminth in MS.

Objective  To determine whether hookworm treatment has effects on magnetic resonance imaging (MRI) activity and T regulatory cells in relapsing MS.

Design, Setting, and Participants  This 9-month double-blind, randomized, placebo-controlled trial was conducted between September 2012 and March 2016 in a modified intention-to-treat population (the data were analyzed June 2018) at the University of Nottingham, Queen’s Medical Centre, a single tertiary referral center. Patients aged 18 to 61 years with relapsing MS without disease-modifying treatment were recruited from the MS clinic. Seventy-three patients were screened; of these, 71 were recruited (2 ineligible/declined).

Interventions  Patients were randomized (1:1) to receive either 25 Necator americanus larvae transcutaneously or placebo. The MRI scans were performed monthly during months 3 to 9 and 3 months posttreatment.

Main Outcomes and Measures  The primary end point was the cumulative number of new/enlarging T2/new enhancing T1 lesions at month 9. The secondary end point was the percentage of cluster of differentiation (CD) 4+CD25highCD127negT regulatory cells in peripheral blood.

Results  Patients (mean [SD] age, 45 [9.5] years; 50 women [71%]) were randomized to receive hookworm (35 [49.3%]) or placebo (36 [50.7%]). Sixty-six patients (93.0%) completed the trial. The median cumulative numbers of new/enlarging/enhancing lesions were not significantly different between the groups by preplanned Mann-Whitney U tests, which lose power with tied data (high number of zeroactivity MRIs in the hookworm group, 18/35 [51.4%] vs 10/36 [27.8%] in the placebo group). The percentage of CD4+CD25highCD127negT cells increased at month 9 in the hookworm group (hookworm, 32 [4.4%]; placebo, 34 [3.9%]; P = .01). No patients withdrew because of adverse effects. There were no differences in adverse events between groups except more application-site skin discomfort in the hookworm group (82% vs 28%). There were 5 relapses (14.3%) in the hookworm group vs 11 (30.6%) receiving placebo.

Conclusions and Relevance  Treatment with hookworm was safe and well tolerated. The primary outcome did not reach significance, likely because of a low level of disease activity. Hookworm infection increased T regulatory cells, suggesting an immunobiological effect of hookworm. It appears that a living organism can precipitate immunoregulatory changes that may affect MS disease activity.

Trial Registration  ClinicalTrials.gov Identifier: NCT01470521

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