15 Jun Stimulating T Cells with Hookworm May Reduce Multiple Sclerosis Relapses
MedicalResearch.com Interview with:
Cris S Constantinescu, MD, PhD, FRCP
Professor, Division of Clinical Neuroscience
Research Group in Clinical Neurology
University of Nottingham
Queen’s Medical Centre
MedicalResearch.com: What is the background for this study?
Response: The study is in some way a test of the hygiene or old friends hypothesis, whereby eradication, through improved hygiene, of some parasites that have existed in the human gut for thousands of years and have suppressed inflammatory reactions, leads to an increase in inflammatory conditions. This has been used to explain the increased autoimmune and inflammatory diseases in the developed world.
Healthy volunteer studies at the University of Nottingham showed therapeutic hookworm infection to be safe and well tolerated up to about 50 larvae, and then safety studies in people with airway hyperreactivity and inflammatory bowel disease raised no concern. Following a study in Argentina showing that people with MS have milder disease when they have a natural co-existing asymptomatic infection with intestinal parasites, we (Professor Pritchard, immunoparasitologist and myself) decided to test hookworm in MS, and for the first time used 25 larvae in a patient study.
MedicalResearch.com: What are the main findings? Is this analogous to BCG vaccination to induce an immune reponse?
Response: In this randomised controlled trial, the total number of new MRI lesions did not differ significantly between patients receiving hookworm and those receiving placebo. However, more than half the patients on hookworm (vs less than a quarter of the patients on placebo) had no lesions at all; so if the statistical analysis had been designed to look at the proportion of patients with no new lesions (an increasingly used outcome measure), the results would have been significant.
In addition, we showed a significant increase in the percentage of regulatory T cells; these are cells that prevent or reduce excessive immune activation and autoimmunity; these cells are deficient in MS, and it appears that the hookworm increases this type of cells which are beneficial in this context.
Hookworm was safe and well tolerated.
MedicalResearch.com: What should readers take away from your report?
Response: A controlled infection with a small number of parasites in MS is safe, induces immunoregulatory responses that may be beneficial for MS and may have some therapeutic benefit. This, however, is modest compared to the current very potent and highly effective disease modifying treatments. Some patients with milder disease or more inclined for natural treatments may consider this.
On the more biological level, it is worth harnessing immunoregulatory mechanisms, for example increasing regulatory T cells in MS (and possibly other autoimmune diseases).
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future studies need to establish whether different protocols can enhance this benefit. For example: would a booster infection at about 9 months enhance the regulatory T cells responses and enhance the clinical/radiological benefit?
Further study may determine the characteristics of patients who developed no new lesions (responders) compared to the fewer who continued accruing new lesions (non-responders) and may allow enriched-design studies targeting those likely to be responders. These can include immunological profiling but also look at differences in the gut microbiota (these latter studies are underway)
Main funding was through the Multiple Sclerosis Society of the UK.
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
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