John Fleming1, Gianna Hernandez2, Leslie Hartman3, Jane Maksimovic3, Sara Nace3, Benjamin Lawler4, Todd Risa5, Thomas Cook6, Rashmi Agni2, Mark Reichelderfer7, Christopher Luzzio1, Loren Rolak4, Aaron Field3, Zsuzsanna Fabry2. 1. Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 2. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 3. Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 4. Department of Neurology, Marshfield Clinic Health System, Marshfield WI, USA. 5. Department of Radiology, Marshfield Clinic Health System, Marshfield WI, USA. 6. Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 7. Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Abstract
BACKGROUND: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. OBJECTIVE: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). METHODS: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. RESULTS: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. CONCLUSION: TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.
BACKGROUND: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. OBJECTIVE: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). METHODS: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. RESULTS: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. CONCLUSION:TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.
Authors: G R Cutter; M L Baier; R A Rudick; D L Cookfair; J S Fischer; J Petkau; K Syndulko; B G Weinshenker; J P Antel; C Confavreux; G W Ellison; F Lublin; A E Miller; S M Rao; S Reingold; A Thompson; E Willoughby Journal: Brain Date: 1999-05 Impact factor: 13.501
Authors: W J Sandborn; D E Elliott; J Weinstock; R W Summers; A Landry-Wheeler; N Silver; M D Harnett; S B Hanauer Journal: Aliment Pharmacol Ther Date: 2013-06-03 Impact factor: 8.171
Authors: Chris H Polman; Stephen C Reingold; Brenda Banwell; Michel Clanet; Jeffrey A Cohen; Massimo Filippi; Kazuo Fujihara; Eva Havrdova; Michael Hutchinson; Ludwig Kappos; Fred D Lublin; Xavier Montalban; Paul O'Connor; Magnhild Sandberg-Wollheim; Alan J Thompson; Emmanuelle Waubant; Brian Weinshenker; Jerry S Wolinsky Journal: Ann Neurol Date: 2011-02 Impact factor: 10.422
Authors: Phurpa Wangchuk; Konstantinos Kouremenos; Ramon M Eichenberger; Mark Pearson; Atik Susianto; David S Wishart; Malcolm J McConville; Alex Loukas Journal: Metabolomics Date: 2019-06-28 Impact factor: 4.290
Authors: A Shemer; S Kivity; O Shovman; T Bashi; O Perry; A Watad; D Ben-Ami Shor; A Volkov; I Barshack; N L Bragazzi; A Krule; M Fridkin; H Amital; M Blank; Y Shoenfeld Journal: Clin Exp Immunol Date: 2018-08 Impact factor: 4.330
Authors: Radu Tanasescu; Christopher R Tench; Cris S Constantinescu; Gary Telford; Sonika Singh; Nanci Frakich; David Onion; Dorothee P Auer; Bruno Gran; Nikos Evangelou; Yasser Falah; Colin Ranshaw; Cinzia Cantacessi; Timothy P Jenkins; David I Pritchard Journal: JAMA Neurol Date: 2020-09-01 Impact factor: 18.302
Authors: Bonnie Douglas; Oyebola Oyesola; Martha M Cooper; Avery Posey; Elia Tait Wojno; Paul R Giacomin; De'Broski R Herbert Journal: Annu Rev Immunol Date: 2021-03-01 Impact factor: 28.527
Authors: Ivet A Yordanova; Friederike Ebner; Axel Ronald Schulz; Svenja Steinfelder; Berit Rosche; Anna Bolze; Friedemann Paul; Henrik E Mei; Susanne Hartmann Journal: Life (Basel) Date: 2021-01-29
Authors: Stephanie M Ryan; Ramon M Eichenberger; Roland Ruscher; Paul R Giacomin; Alex Loukas Journal: PLoS Pathog Date: 2020-05-14 Impact factor: 6.823