Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study

Abstract

Background Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. Objective To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Methods Five subjects with newly diagnosed, treatment-naive relapsing–remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. Results The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. Conclusion TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Helminth Infection and Type 1 Diabetes

“…Whereas large, randomized and well-controlled trials of helminth therapy are underway on the heels of positive initial studies of T. suis in Crohn's disease, ulcerative colitis, and MS [107,109,110]. Similar investigation in T1D has lagged behind.…”

“…These observations from naturally infected patients supported the investigation of therapeutic helminth infection of relapsing-remitting MS patients in a recently completed clinical study. Biweekly oral administration of 2,500 ova of the porcine whipworm, Trichuris suis, to a small cohort of MS patients over a 3-month treatment period reduced new gadolinium-enhancing lesions detected by magnetic resonance imaging relative to baseline, and induced an increase in regulatory IL-10 detected in serum; these effects returned to baseline within 2 months of cessation of T. suis ova therapy [107]. Although these data are from small, exploratory clinical studies, they are supportive of the potential of helminth-derived therapies in MS, and have paved the way for larger, double-blind, placebocontrolled trials.…”

Evolutionary medicine: its scope, interest and potential

“…When, after 5 years, one patient started to suffer from the worm infection and was treated with anti-helminthics, his multiple sclerosis symptoms rapidly worsened, rising within a year to equal those of the patients who had no worm infection. Such observations, coupled with experiments on mouse models [39,40], inspired a phase 1 clinical trial using eggs of pig whipworms, Trichuris suis, chosen because they elicit immune responses in the human gut without establishing a damaging infection [42,43]. In that small sample, the patients either improved or did not get worse during worm therapy.…”

Environmental Factors and Type 1 Diabetes Mellitus in Pediatric Age Group

“…Modification of the immune system in knocked out MyD88 seriously impairs the interactions between the immune system and microbiota. Due to these positive results after treatments with a mycobacterium extract [65], helminthiases treatment and probiotics [66,67] in patients with atopic dermatitis and multiple sclerosis, have recently been reported [68,69]. Instead, vaccination with bacille Calmette-Guèrin produced negative results in patient with T1DM [70,71].…”