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

Tanasescu, Radu; Tench, Christopher R.; Constantinescu, Cris S.; Telford, Gary; Singh, Sonika; Frakich, Nanci; Onion, David; Auer, Dorothee P.; Gran, Bruno; Evangelou, Nikos; Falah, Yasser; Ranshaw, Colin; Cantacessi, Cinzia; Jenkins, Timothy P.; Pritchard, David I.

Abstract

© 2020 American Medical Association. All rights reserved. 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.

Citation

Tanasescu, R., Tench, C. R., Constantinescu, C. S., Telford, G., Singh, S., Frakich, N., …Pritchard, D. I. (2020). Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial. JAMA Neurology, 77(9), 1089-1098. https://doi.org/10.1001/jamaneurol.2020.1118

• Journal Article Type: Article
• Acceptance Date: Feb 4, 2020
• Online Publication Date: Jun 15, 2020
• Publication Date: Jun 15, 2020
• Deposit Date: Feb 6, 2020
• Journal: JAMA Neurology
• Print ISSN: 2168-6149
• Electronic ISSN: 2168-6157
• Publisher: American Medical Association
• Peer Reviewed: Peer Reviewed
• Volume: 77
• Issue: 9
• Pages: 1089-1098
• DOI: https://doi.org/10.1001/jamaneurol.2020.1118
• Keywords: multiple sclerosis, helminths, hookworm, regulatory T cells
• Public URL: https://nottingham-repository.worktribe.com/output/3910049
• Publisher URL: https://jamanetwork.com/journals/jamaneurology/article-abstract/2767084