Hookworms associated with possible immunobiological effect for the treatment of relapsing multiple sclerosis

1. Hookworms was found to be a safe and well tolerated treatment option possibly associated with an immunobiological effect in relapsing multiple sclerosis.

Evidence Rating Level: 2 (Good)

Multiple sclerosis (MS), an immune-mediated central nervous system disease, is associated with an imbalance between inflammatory cytokines and immunoregulatory factors, namely regulatory T cells (Tregs). Compared to matched uninfected MS controls over 5 years, MS patients naturally infected with gastrointestinal parasites have milder disease, which is associated with higher Treg activity.  Some small, non-placebo-controlled, short duration studies have found patients infected with N americanus larvae to have favourable MRI and immunological outcomes in their autoimmune and allergic conditions. In this 9 month, double-blind, placebo-controlled trial, 71 patients were randomized in a 1:1 ratio to receive either experimental infection with 25 N americanus L3 larvae (HW treatment) or placebo (pharmacopoeial-grade water). At baseline, there was no difference between the groups in T2 lesion load and there was a  higher percentage of T cells in the placebo than the HW arm. At nine months, there was no significant difference in new, enlarging, or enhancing brain lesions between the groups (154 in HW, 164 in placebo) at 9 months, while there was a higher number of scans without detectable MRI activity in the treatment group (51% vs 28% placebo). There was an increase in Tregs in the HW arm and a decrease in the placebo group, without reaching significance, and four patients in the HW arm compared to 10 in placebo experienced relapses during the trial. No patients withdrew because of adverse effects from the HW infection and there were no differences in adverse effects between groups next to initial skin discomfort when the worms were applied to the arm (82% vs 28%). This trial showed that treatment with hookworm was safe and well-tolerated, with the increased Treg count suggesting a possible immunobiological effect despite no difference in the primary outcome of lesions between groups. Further study with a design and sample powered to compare the proportion of patients without disease activity and a longer treatment duration (1-2 years) would be needed to assess clinical response, but preliminary findings are promising for a potential new therapeutic option in the future.

Click to read the study in JAMA Neurology

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