Development of Therapies for Celiac Disease C O N F E R E N
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Celiac Disease and Nonceliac Gluten Sensitivitya Review
Clinical Review & Education JAMA | Review Celiac Disease and Nonceliac Gluten Sensitivity A Review Maureen M. Leonard, MD, MMSc; Anna Sapone, MD, PhD; Carlo Catassi, MD, MPH; Alessio Fasano, MD CME Quiz at IMPORTANCE The prevalence of gluten-related disorders is rising, and increasing numbers of jamanetwork.com/learning individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. OBSERVATIONS Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial). Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, extraintestinal signs or symptoms, or both, Author Affiliations: Center for Celiac suggesting that celiac disease is a systemic disease. Nonceliac gluten sensitivity Research and Treatment, Division of is diagnosed in individuals who do not have celiac disease or wheat allergy but who Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion Children, Boston, Massachusetts of gluten-containing grains, with symptomatic improvement on their withdrawal. The (Leonard, Sapone, Catassi, Fasano); clinical variability and the lack of validated biomarkers for nonceliac gluten sensitivity make Celiac Research Program, Harvard establishing the prevalence, reaching a diagnosis, and further study of this condition Medical School, Boston, Massachusetts (Leonard, Sapone, difficult. Nevertheless, it is possible to differentiate specific gluten-related disorders from Catassi, Fasano); Shire, Lexington, other conditions, based on currently available investigations and algorithms. -
Study Design to Validate Biomarkers of Therapeutic Response in NASH Due to Cirrhosis
Study Design to Validate Biomarkers of Therapeutic Response in NASH Due to Cirrhosis Detlef Schuppan Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center Mainz, Germany Division of Gastroenterology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, USA International Workshop on NASH Biomarkers, Washington, DC, May 18-19, 2018 HARVARD Research MEDICAL Center for SCHOOL Institute for Translational Immunology Immune Therapy No Conflict of Interest to Declare Related to this Presentation Fibrosis Progression and Reversal in NASH Inflammation, the reparative response and evolution of fibrosis/cirrhosis in NASH Fibrogenesis • is a waxing and waning process A • follows inflammation (reparative response) inflammation fibrosis Severity Time B Severity Time Antifibrotic therapy C cirrhosis Severity Time Schuppan et al, J Hepatol 2018 Fibrogenesis in NASH Ox. stress, ROS normal liver macrophage Insulin resistance, FFA Toxins repetitive damage MF Toxic bile salts (multiple hits) T (Auto-) Immunity HBV, HCV genetic Microbiome, nutrients quiescent predisposition stellate cell (lipoapoptotic) hepatocytes activated cholangiocytes endothelium fibrotic liver portal or collagen- Cirrhosis perivascular synthesis fibroblast organ MMP-1/3/13 failure activated matrix accumulation myofibroblast TIMP-1 Cirrhosis and HCC HSC TIMP-2 Schuppan and Afdhal, Lancet 2008 common pathways & Schuppan and Kim, JCI 2013 immune environment ! Inhibition of fibrogenesis - induction of fibrolysis normal -
Celiac Disease and Nonceliac Gluten Sensitivity a Review
Clinical Review & Education JAMA | Review Celiac Disease and Nonceliac Gluten Sensitivity A Review Maureen M. Leonard, MD, MMSc; Anna Sapone, MD, PhD; Carlo Catassi, MD, MPH; Alessio Fasano, MD CME Quiz at IMPORTANCE The prevalence of gluten-related disorders is rising, and increasing numbers of jamanetwork.com/learning individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. OBSERVATIONS Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial). Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, extraintestinal signs or symptoms, or both, Author Affiliations: Center for Celiac suggesting that celiac disease is a systemic disease. Nonceliac gluten sensitivity Research and Treatment, Division of is diagnosed in individuals who do not have celiac disease or wheat allergy but who Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion Children, Boston, Massachusetts of gluten-containing grains, with symptomatic improvement on their withdrawal. The (Leonard, Sapone, Catassi, Fasano); clinical variability and the lack of validated biomarkers for nonceliac gluten sensitivity make Celiac Research Program, Harvard establishing the prevalence, reaching a diagnosis, and further study of this condition Medical School, Boston, Massachusetts (Leonard, Sapone, difficult. Nevertheless, it is possible to differentiate specific gluten-related disorders from Catassi, Fasano); Shire, Lexington, other conditions, based on currently available investigations and algorithms. -
Outcome Measures in Coeliac Disease Trials
Downloaded from http://gut.bmj.com/ on March 30, 2018 - Published by group.bmj.com Gut Online First, published on February 13, 2018 as 10.1136/gutjnl-2017-314853 Coeliac disease ORIGINAL ARTICLE Outcome measures in coeliac disease trials: the Tampere recommendations Jonas F Ludvigsson,1,2 Carolina Ciacci,3 Peter HR Green,4 Katri Kaukinen,5,6 Ilma R Korponay-Szabo,7,8 Kalle Kurppa,9,10 Joseph A Murray,11 Knut Erik Aslaksen Lundin,12,13 Markku J Maki,14,15 Alina Popp,16,17 Norelle R Reilly,18,19 Alfonso Rodriguez-Herrera,20 David S Sanders,21 Detlef Schuppan,22,23 Sarah Sleet,24 Juha Taavela,25 Kristin Voorhees,26 Marjorie M Walker,27 Daniel A Leffler28 ► Additional material is ABSTRact published online only. To view, Objective A gluten-free diet is the only treatment Significance of this study please visit the journal online option of coeliac disease, but recently an increasing (http:// dx. doi. org/ 10. 1136/ What is already known about this subject? gutjnl- 2017- 314853). number of trials have begun to explore alternative treatment strategies. We aimed to review the literature ► A gluten-free diet is the only treatment option For numbered affiliations see of coeliac disease, but recently an increasing end of article. on coeliac disease therapeutic trials and issue recommendations for outcome measures. number of trials have begun to explore alternative treatment strategies. Correspondence to Design Based on a literature review of 10 062 Dr Jonas F Ludvigsson, references, we (17 researchers and 2 patient ► A large number of trials of non-dietary Department of Medical representatives from 10 countries) reviewed the use treatments for coeliac disease are ongoing or Epidemiology and Biostatistics, and suitability of both clinical and non-clinical outcome under way. -
A Common Dietary Component Wheat Amylase Trypsin Inhibitors As Drivers of Chronic Liver Disease in Pre-Clinical Models of NASH and Liver Fibrosis
A Common Dietary Component Wheat Amylase Trypsin Inhibitors as Drivers of Chronic Liver Disease in Pre-Clinical Models of NASH and Liver Fibrosis Muhammad Ashfaq-Khan1, Misbah Aslam1,2, Muhammad Asif Qureshi3, Marcel Senkowski1, Shih Yen-Weng1, Yong Ook Kim1, Jörn M. Schattenberg4, Detlef Schuppan*1,4 1Institute of Translational Immunology, University Medical Center, Mainz, Germany 2 Shaheed Benazir Bhutto Women University, Peshawar, Pakistan 3 Dow University Medical Sciences, Karachi, Pakistan 4 Division of Gastroenterology, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, US. BACKGROUND & AIMS Proinflammatory gene expressions and immunohistochemistry of epididymal fat LFD HFD The gut-liver-axis has emerged an important Weight base indices driver of chronic liver disease. In line with this, specific food derived (non-tolerable) immunogenic Poster presented at: presented Poster HFD/G/ATI HFD/ATI signals from the gut are potentially the important CLSs CD68+ contributors in worsening obesity and non- alcoholic fatty liver disease (NAFLD) and liver fibrosis. A common immunogenic component in food staple (that resist to intestinal degradation) are wheat amylase trypsin inhibitors (ATI) that activate intestinal macrophages and dendritic cells via toll like receptor-4 migrate and propagate the inflammatory stimulus to the peripheral organs such as liver. We therefore studied how far nutritional ATI would affect NAFLD and liver Non alcoholic steatohepatitis (NAS) score fibrosis in preclinical models of NASH and liver A HFD HFD/G/ATI HFD/ATI fibrosis. LFD DOI: 10.3252/pso.eu.ILC2019.2019 METHOD 20x . Male C57BI/6J mice received a carbohydrate and protein 40x (zein) defined low fat or high fat diet (HFD), with or without 30% of the protein being replaced by wheat E B LFD HFD gluten (G, naturally containing 0.15g ATI per 10g), or 0.7% of the zein as purified ATI for 8 weeks. -
Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition During Biliary Fibrosis in Rodents and Humans
Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans Alessia Omenetti, … , Detlef Schuppan, Anna Mae Diehl J Clin Invest. 2008;118(10):3331-3342. https://doi.org/10.1172/JCI35875. Research Article Epithelial-mesenchymal transitions (EMTs) play an important role in tissue construction during embryogenesis, and evidence suggests that this process may also help to remodel some adult tissues after injury. Activation of the hedgehog (Hh) signaling pathway regulates EMT during development. This pathway is also induced by chronic biliary injury, a condition in which EMT has been suggested to have a role. We evaluated the hypothesis that Hh signaling promotes EMT in adult bile ductular cells (cholangiocytes). In liver sections from patients with chronic biliary injury and in primary cholangiocytes isolated from rats that had undergone bile duct ligation (BDL), an experimental model of biliary fibrosis, EMT was localized to cholangiocytes with Hh pathway activity. Relief of ductal obstruction in BDL rats reduced Hh pathway activity, EMT, and biliary fibrosis. In mouse cholangiocytes, coculture with myofibroblastic hepatic stellate cells, a source of soluble Hh ligands, promoted EMT and cell migration. Addition of Hh-neutralizing antibodies to cocultures blocked these effects. Finally, we found that EMT responses to BDL were enhanced in patched-deficient mice, which display excessive activation of the Hh pathway. Together, these data suggest that activation of Hh signaling promotes EMT and contributes to the evolution of biliary fibrosis during chronic cholestasis. Find the latest version: https://jci.me/35875/pdf Related Commentary, page 3263 Research article Hedgehog signaling regulates epithelial- mesenchymal transition during biliary fibrosis in rodents and humans Alessia Omenetti,1 Alessandro Porrello,2 Youngmi Jung,1 Liu Yang,1 Yury Popov,3,4 Steve S. -
Sensitivities to Wheat? Gluten Might Not Be to Blame
Recently published research suggests that there may be a previously unknown protein in wheat which may be causing the symptoms we have associated with gluten in the past: Amylase- Trypsin Inhibitors (ATIs). Sensitivities to Wheat? Gluten Might Not Be to Blame What you've heard about gluten might be wrong. This article originally appeared on Medical Daily. Gluten may not be the culprit when it comes to wheat sensitivities, according to a new body of research presented at the United European Gastroenterology Week 2016. Instead, a team of scientists from Johannes Gutenberg University in Germany discovered a different protein in wheat known as amylase-trypsin inhibitors (ATIs), which may be what triggers stomach- sickening inflammation and other symptoms. The whole grains/gluten situation and its potential impact on health issues appears to be developing much more complexity than was previously understood: recent research in Australia identified dozens of proteins in wheat that have previously not been known, and many of these may in fact be more detrimental than those that are typically tested for (and there are currently no lab tests available for these proteins). (We were unable to locate the published research for this Australian paper by our publishing deadline, but we will continue to search for it and hopefully include it in a future newsletter). Biotics offers a number of formulations targeted towards the GI system: A.D.P. (Anti-Dysbiosis Product) 60T Berberine HCl May help activate AMPK Bio-HPF CANADA (H-Pylori Factor) May help activate AMPK BioDoph-7 Plus BioDophilus Caps BioDophilus-FOS Bromelain Plus CLA Caprin 100C FC-Cidal GamOctaPro (Powder) Gastrazyme HCL-Plus IAG Intenzyme Forte (Trypsin & Alpha Chymotrypsin) IPS Canada (Intestinal Permeability Support) L-Glutamine Caps L-Glutamine Powder Lactozyme Irrespective of the specific proteins in wheat and other grains that cause health issues, we all know that grains in general and some specific grains in particular (wheat, rye and barley). -
Zedira Communication
Press release __________________________________________________________________________ Zedira, Dr. Falk Pharma and the University of Mainz Hospital, which together comprise a flagship project of the Ci3 leading-edge cluster, are to receive additional subsidy funding for clinical development of a celiac disease drug. __________________________________________________________________________ Darmstadt, Freiburg, Mainz 20 October 2015 The consortium consisting of Zedira, Dr. Falk Pharma and Prof. Schuppan of the Institute of Translational Immunology and the Department of Medicine at the Johannes Gutenberg University in Mainz has announced that their collaboration on drug development of celiac disease is being further supported under the Ci3 excellence cluster of the German Federal Ministry for Education and Research (German abbreviation: BMBF). The project involves the clinical development of the ZED1227 drug candidate. ZED1227 is the first low-molecular tissue transglutaminase blocker in the clinics. The joint venture was started as a flagship project of the leading-edge cluster for individualized immuneintervention (Ci3). Celiac Disease is the most common chronic inflammation of the small intestine, with a worldwide prevalence around 1% in most countries. The autoimmune disease is triggered and maintained by alimentary gluten in genetically susceptible individuals. About Zedira: The Darmstadt-based biotech company focuses on celiac disease and consequently also on the transglutaminase family of enzymes. The Company develops, produces and markets products for research and development as well as for diagnostics. Based on its patented family of low-molecular transglutaminase blockers, Zedira is establishing an active ingredient pipeline covering the primary indication of celiac disease. As an area of secondary indication the company is working on new approaches to thrombosis prophylaxis. Further, Zedira is working on bioavailable tissue transglutaminase inhibitors to address fibrotic diseases, e.g. -
January 2021 Alert
January 2021 Alert Items 1-187 1. Epidemiology, Presentation, and Diagnosis of Celiac Disease Gastroenterology. 2021 Jan;160(1):63-75. doi: 10.1053/j.gastro.2020.06.098. Epub 2020 Sep 18. Authors Benjamin Lebwohl 1 , Alberto Rubio-Tapia 2 Affiliations • 1 Department of Medicine, Columbia University Irving Medical Center, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York. Electronic address: [email protected]. • 2 Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio. • PMID: 32950520 • DOI: 10.1053/j.gastro.2020.06.098 Abstract The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. -
From Ptolemaus to Copernicus: the Evolving System of Gluten-Related Disorder
nutrients From Ptolemaus to Copernicus: The Evolving System of Gluten-Related Disorder Edited by Carlo Catassi and Alessio Fasano Printed Edition of the Special Issue Published in Nutrients www.mdpi.com/journal/nutrients From Ptolemaus to Copernicus: The Evolving System of Gluten-Related Disorder Special Issue Editors Carlo Catassi Alessio Fasano MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editors Carlo Catassi Universita` Politecnica delle Marche Italy Alessio Fasano Massachusetts General Hospital East USA Editorial Office MDPI AG St. Alban-Anlage 66 Basel, Switzerland This edition is a reprint of the Special Issue published online in the open access journal Nutrients (ISSN 2072-6643) from 2016–2017 (available at: http://www.mdpi.com/journal/nutrients/special issues/ evolving system gluten disorders). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: Lastname, F.M.; Lastname, F.M. Article title. Journal Name. Year. Article number, page range. First Edition 2018 ISBN 978-3-03842-731-5 (Pbk) ISBN 978-3-03842-732-2 (PDF) Articles in this volume are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book taken as a whole is c 2018 MDPI, Basel, Switzerland, distributed under the terms and conditions of the Creative Commons license CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). -
The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): an Update
nutrients Review The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update Carlo Catassi 1, Armin Alaedini 2, Christian Bojarski 3, Bruno Bonaz 4, Gerd Bouma 5, Antonio Carroccio 6 ID , Gemma Castillejo 7 ID , Laura De Magistris 8, Walburga Dieterich 9, Diana Di Liberto 10, Luca Elli 11, Alessio Fasano 12, Marios Hadjivassiliou 13, Matthew Kurien 14 ID , Elena Lionetti 1, Chris J. Mulder 5, Kamran Rostami 15, Anna Sapone 12, Katharina Scherf 16, Detlef Schuppan 17, Nick Trott 14, Umberto Volta 18, Victor Zevallos 17, Yurdagül Zopf 9 and David S. Sanders 14,* 1 Department of Pediatrics, Marche Polytechnic University, 60121 Ancona, Italy; [email protected] (C.C.); [email protected] (E.L.) 2 Department of Medicine, Columbia University Medical Center, New York, NY 10027, USA; [email protected] 3 Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité, Campus Benjamin Franklin, 12203 Berlin, Germany; [email protected] 4 Department of Gastroenterology and Liver Diseases, CHU, 38043 Grenoble, France; [email protected] 5 Celiac Center Amsterdam, Department of Gastroenterology, VU University Medical Center, 1117 Amsterdam, The Netherlands; [email protected] (G.B.); [email protected] (C.J.M.) 6 Department of Internal Medicine, “Giovanni Paolo II” Hospital, Sciacca (AG) and University of Palermo, 92019 Sciacca, Italy; [email protected] 7 Paediatric Gastroenterology Unit, Sant Joan de Reus University Hospital. IISPV, -
What Wikipedia Can't Tell You About Celiac Disease Prevention
What Wikipedia Can’t Tell You About Celiac Disease Prevention: Hear it from the Experts With Alessio Fasano, M.D., Carlo Catassi, M.D., and Sabine Vriezinga, M.D. facebook.com/nfceliacawareness NATIONAL FOUNDATION FOR CELIAC AWARENESS @CeliacAwareness www.CeliacCentral.org/webinars www.CeliacCentral.org/webinars www.CeliacCentral.org © 2015 All Rights Reserved. 1 Important Reminders! ① Will this information be available at a later date? • Yes, always! • Webinar recording will be posted along with the webinar slides within 72 hours after the live webinar ends at CeliacCentral.org/webinars/archive/ ② Are continuing education credits available? • Yes! • Attendees must complete the follow-up survey in order to access this certificate. – The follow-up survey will be sent on Thursday, April 30th through an email from NFCA. • To ensure that you receive this email, make sure that NFCA ([email protected]) is on your allowed senders list. – Accidentally unsubscribed? Register for the webinar with a new email address – Be sure your email address is spelled correctly when registering • Continuing education credits given for live viewers only – We encourage you to check out our archived webinars, but note that continuing education credit will not be given • In the case of group viewing, only the registered and logged in participant will receive credit facebook.com/nfceliacawareness NATIONAL FOUNDATION FOR CELIAC AWARENESS @CeliacAwareness www.CeliacCentral.org/webinars www.CeliacCentral.org/webinars www.CeliacCentral.org