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Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation

INTRODUCTION: EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of comm...

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Autores principales: Itano, Andrea, Maslin, Douglas, Ramani, Kritika, Mehraei, Golbarg, Carpenter, Nancy, Cormack, Taylor, Saghari, Mahdi, Moerland, Matthijs, Troy, Erin, Caffry, Will, Wardwell-Scott, Leslie, Abel, Stuart, McHale, Duncan, Bodmer, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197930/
https://www.ncbi.nlm.nih.gov/pubmed/37215725
http://dx.doi.org/10.3389/fmed.2023.1070433
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author Itano, Andrea
Maslin, Douglas
Ramani, Kritika
Mehraei, Golbarg
Carpenter, Nancy
Cormack, Taylor
Saghari, Mahdi
Moerland, Matthijs
Troy, Erin
Caffry, Will
Wardwell-Scott, Leslie
Abel, Stuart
McHale, Duncan
Bodmer, Mark
author_facet Itano, Andrea
Maslin, Douglas
Ramani, Kritika
Mehraei, Golbarg
Carpenter, Nancy
Cormack, Taylor
Saghari, Mahdi
Moerland, Matthijs
Troy, Erin
Caffry, Will
Wardwell-Scott, Leslie
Abel, Stuart
McHale, Duncan
Bodmer, Mark
author_sort Itano, Andrea
collection PubMed
description INTRODUCTION: EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body. METHODS: Supported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model. RESULTS: Preclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation. DISCUSSION: This is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation. Clinical Trial Registration: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.
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spelling pubmed-101979302023-05-20 Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation Itano, Andrea Maslin, Douglas Ramani, Kritika Mehraei, Golbarg Carpenter, Nancy Cormack, Taylor Saghari, Mahdi Moerland, Matthijs Troy, Erin Caffry, Will Wardwell-Scott, Leslie Abel, Stuart McHale, Duncan Bodmer, Mark Front Med (Lausanne) Medicine INTRODUCTION: EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body. METHODS: Supported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model. RESULTS: Preclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation. DISCUSSION: This is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation. Clinical Trial Registration: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl. Frontiers Media S.A. 2023-05-05 /pmc/articles/PMC10197930/ /pubmed/37215725 http://dx.doi.org/10.3389/fmed.2023.1070433 Text en Copyright © 2023 Itano, Maslin, Ramani, Mehraei, Carpenter, Cormack, Saghari, Moerland, Troy, Caffry, Wardwell-Scott, Abel, McHale and Bodmer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Itano, Andrea
Maslin, Douglas
Ramani, Kritika
Mehraei, Golbarg
Carpenter, Nancy
Cormack, Taylor
Saghari, Mahdi
Moerland, Matthijs
Troy, Erin
Caffry, Will
Wardwell-Scott, Leslie
Abel, Stuart
McHale, Duncan
Bodmer, Mark
Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
title Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
title_full Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
title_fullStr Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
title_full_unstemmed Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
title_short Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
title_sort clinical translation of anti-inflammatory effects of prevotella histicola in th1, th2, and th17 inflammation
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197930/
https://www.ncbi.nlm.nih.gov/pubmed/37215725
http://dx.doi.org/10.3389/fmed.2023.1070433
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