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Celiac.com 09/16/2024 - Celiac disease is an autoimmune condition that affects individuals when they consume gluten, a protein found in wheat, barley, and rye. In those with the disease, the ingestion of gluten triggers an immune response that damages the small intestine. One of the key enzymes involved in this process is transglutaminase 2, which modifies gluten peptides, making them more likely to cause inflammation. This study focuses on a new therapeutic approach using a transglutaminase 2 inhibitor called ZED1227, which aims to reduce gluten-induced damage in individuals with celiac disease. Objective of the Study The main goal of the study was to investigate how effective the transglutaminase 2 inhibitor ZED1227 is at preventing gluten-induced damage in the intestines of people with celiac disease. Participants in the study had been on a gluten-free diet for a long time but were given a six-week gluten challenge while also taking either ZED1227 or a placebo. Researchers analyzed biopsies from the small intestine before and after this period to assess the molecular effects of ZED1227 and its potential to protect against gluten-induced damage. Mechanism of Action Transglutaminase 2 plays a central role in celiac disease by modifying gluten peptides, making them more reactive to the immune system. This reaction leads to the activation of immune cells that cause inflammation and damage to the intestinal lining. The inhibitor ZED1227 works by blocking the activity of this enzyme, which theoretically should prevent the gluten peptides from triggering the harmful immune response. The study sought to confirm this effect at the molecular level by analyzing the genetic activity in the intestinal cells of participants. Study Methodology Participants with celiac disease were divided into two groups. Both groups underwent a gluten challenge, meaning they consumed gluten for six weeks. One group received a daily dose of ZED1227, while the other group received a placebo. Duodenal biopsies were taken from the participants both before and after the gluten challenge, and researchers performed a detailed analysis of the gene expression in these tissue samples. Key Findings The results of the study were significant. The researchers found that ZED1227 effectively prevented the majority of the harmful gene activity that gluten normally triggers in people with celiac disease. In particular, the treatment preserved the structure and function of the intestinal lining. One of the key findings was that ZED1227 blocked the immune response driven by interferon-gamma, a molecule that plays a major role in the inflammation seen in celiac disease. By inhibiting this pathway, ZED1227 protected the intestines from gluten-induced damage, including villous atrophy (the flattening of the intestinal surface) and crypt hyperplasia (an abnormal increase in the depth of the intestinal lining). Genetic Considerations The study also highlighted the role of genetics in how individuals respond to gluten. Specifically, it showed that people with certain genetic variants related to human leukocyte antigen DQ2 were more sensitive to gluten. These individuals, who carry a homozygous form of the gene, had a more intense immune response to gluten, even when taking ZED1227. This suggests that genetic factors could influence how well individuals respond to treatments like ZED1227, and some people may require higher doses or longer treatment durations to achieve optimal protection. Potential Benefits for Celiac Patients For individuals with celiac disease, the only current treatment is a strict gluten-free diet. However, following such a diet is challenging and does not always fully prevent gluten exposure or intestinal damage. This study suggests that ZED1227 could offer a new therapeutic option for these patients. By inhibiting transglutaminase 2, ZED1227 could prevent the damage caused by accidental gluten ingestion, providing an additional layer of protection for those who are highly sensitive to gluten or struggle to maintain a perfectly gluten-free diet. Study Limitations and Future Directions While the findings of this study are promising, the researchers noted a few limitations. The study involved a relatively small number of participants, and further research with larger groups will be needed to confirm the results. Additionally, the study only tested one dose of ZED1227, and future studies may explore whether higher or lower doses are more effective for different genetic subgroups of patients. Another area of interest for future research is the long-term safety and effectiveness of ZED1227. The six-week gluten challenge provided valuable insights, but longer-term studies will be necessary to understand how the treatment works over months or even years. The researchers also suggested that a more personalized approach to treatment, where doses of ZED1227 are tailored to individual genetic profiles, could enhance the effectiveness of the therapy. Conclusion and Implications for Celiac Patients This study presents a hopeful new direction for the treatment of celiac disease. ZED1227, by inhibiting transglutaminase 2, shows strong potential to prevent the intestinal damage caused by gluten. For those with celiac disease, this could mean fewer symptoms, less inflammation, and overall better intestinal health, even in cases of accidental gluten exposure. While more research is needed to confirm the long-term benefits and fine-tune the treatment for different genetic profiles, ZED1227 represents a promising step toward improving the quality of life for people with celiac disease. Read more at: nature.com

Celiac.com 02/05/2024 - Celiac disease is a condition triggered by gluten consumption in susceptible individuals, and which has long posed challenges for those affected. However, a new study has illuminated a potential guardian in the microbial world that could shield against the gut disruptions caused by gluten. The study team included Tina Tran, Stefania Senger, Mariella Baldassarre, Rachel A. Brosnan, Fernanda Cristofori, Marco Crocco, Stefania De Santis, Luca Elli, Christina S. Faherty, Ruggero Francavilla, Isabella Goodchild-Michelman, Victoria A. Kenyon, Maureen M. Leonard, Rosiane S. Lima, Federica Malerba, Monica Montuori, Annalisa Morelli, Lorenzo Norsa, Tiziana Passaro, Pasqua Piemontese, James C. Reed, Naire Sansotta, Francesco Valitutti, Ali R. Zomorrodi, and the CDGEMM Team. Their novel research focuses on Bacteroides vulgatus, a bacterial species known for its anti-inflammatory properties, and its impact on maintaining the integrity of the human celiac gut. Researchers Single Out Bacteroides Vulgatus' Protective Effect The study, conducted by a dedicated team of researchers, initially observed a decreased presence of microbial species with potential anti-inflammatory properties in individuals developing celiac disease compared to those who did not. This led the researchers to hone in on Bacteroides vulgatus, aiming to establish its protective role and understand how its byproducts could counteract gluten-induced changes in human gut epithelial functions. To delve into this, the researchers identified, isolated, cultivated, and sequenced a unique strain, named 20220303-A2, of B. vulgatus found exclusively in control subjects. Using a human gut organoid system developed from pre-celiac patients, they closely monitored the epithelial phenotype and innate immune cytokines under various conditions: baseline, after exposure to gliadin (a component of gluten), and after exposure to both gliadin and B. vulgatus cell-free supernatant (CFS). The results were striking. After gliadin exposure, there were noticeable increases in epithelial cell death, epithelial monolayer permeability, and the secretion of pro-inflammatory cytokines—typical hallmarks associated with celiac disease. However, when the organoids were exposed to B. vulgatus 20220303-A2 CFS, these adverse effects were significantly mitigated. Remarkably, the protective effects were linked to epigenetic reprogramming of the treated organoids, suggesting a sophisticated mechanism at play. The study underscores the significance of gut microbiota in the context of celiac disease, emphasizing that alterations in microbial composition may precede the onset of the condition in genetically susceptible individuals. The dysbiosis observed in these individuals is characterized by a decline in protective bacterial strains, such as B. vulgatus. In summary, this research not only identifies a unique strain of Bacteroides vulgatus with potential protective properties, but also sheds light on the intricate mechanisms by which it shields the gut epithelium from the disruptions from gluten. Exactly what, if any new avenues for understanding and, potentially, managing celiac disease, are opened by this research, remains to be seen. Exactly what hope this may offer for those navigating the complexities of a gluten-free lifestyle, also remains unclear. Stay tuned for more on this, and related, celiac disease and gluten-free developments. Read more in Nature

Celiac.com 06/27/2024 - For people with celiac disease who are attempting to maintain a gluten-free diet, there are some potential new treatment options on the horizon. Managing celiac disease means adhering to a strict gluten-free diet. Many people with celiac disease, who are attempting to maintain a gluten-free diet, continue to have regular or intermittent symptoms. In fact, research shows that is estimated that up to 50% of celiac disease patients have persistent symptoms while on the gluten-free diet. The most common reason for persistent symptoms is continuing to ingest gluten, often by accident. A clinical trial is currently evaluating the effectiveness of TAK-062 in reducing symptoms and improving small intestinal damage caused by gluten exposure. Here's what you need to know. Study Aim The main aim of the trial is to see how well TAK-062 reduces celiac-related symptoms, and improves small intestinal damage from gluten exposure, in people with celiac disease. Participants will receive either TAK-062 or a placebo to measure its impact against the control group. New Study on TAK-062 for Celiac Disease A new clinical trial is testing TAK-062, a potential treatment for people with celiac disease who are trying to follow a gluten-free diet. Here are the main points about who can join and who can't. Who Can Join the Study? Understanding of GFD: You need to know a lot about gluten-free diets. This will be checked by a test and confirmed by the study investigator. Symptoms: You must have at least one moderate or severe celiac-related symptom on three or more days in a week during the screening period. Diet History: You should have been trying to follow a gluten-free diet for at least 12 months. Intestinal Damage: You must have small intestinal damage, shown by a specific measure from a biopsy. Genetic Markers: You need to have the HLA-DQ2 and/or HLA-DQ8 genetic markers. Overall Health: You should be in good health based on a medical check-up. Body Mass Index (BMI): Your BMI should be between 16 and 45 kg/m². Consistency: You must be able to keep the same diet and medication routines during the study. Who Can't Join the Study? Other GI Disorders: If you have other inflammatory gut diseases or uncontrolled autoimmune diseases, you can't join. Immunosuppressant Use: If you’ve used systemic immunosuppressants or corticosteroids recently, you’re not eligible. Digestive Supplements: Using over-the-counter digestive enzymes or supplements for gluten digestion disqualifies you, except for lactase. Symptom Diary: You need to complete at least 75% of the symptom diary during the run-in period. Microscopic Colitis: Active microscopic colitis or a recent history of it disqualifies you. Refractory celiac disease: If you have type 2 refractory celiac disease or ulcerative jejunitis, you can't join. NSAIDs: Chronic use of NSAIDs, except for low-dose aspirin, disqualifies you. Villous Abnormalities: Using medications that cause villous damage means you can't join. Recent GI Treatments: Recent use of certain GI treatments or supplements disqualifies you. Severe Infections: A severe enteric infection in the past six months disqualifies you. Endoscopy Issues: If you can’t have an endoscopy, you can’t join. Food Allergies: Allergies to ingredients in the study food bar disqualify you. Drug Reactions: History of reactions to aminoglycosides disqualifies you. Infections: HIV, hepatitis B or C infections disqualify you. COVID-19: Testing positive for COVID-19 with symptoms that affect the study disqualifies you. Wheat/Gluten Allergy: Known wheat or gluten allergies disqualify you. Ingredient Sensitivity: Sensitivity to TAK-062 or placebo ingredients disqualifies you. Active Cancer: Current or recent cancer treatment disqualifies you, except for certain early-stage cancers. This trial is another of many that offers hope for a new therapeutic approach for managing celiac disease, potentially improving the quality of life for many individuals struggling with this condition. Find more information at classic.clinicaltrials.gov

Celiac.com 05/03/2024 - In February 2019, a young woman named Chelsea received a life-changing diagnosis: celiac disease. Reflecting on her past, she realized that the signs of this condition had been present even during her high school years. Initially, she dismissed feelings of bloating and discomfort after consuming foods like pizza and pasta as the result of indulging in too much junk food. However, as she entered adulthood and began her career, her health began to deteriorate rapidly. The bloating became frequent and painful, accompanied by persistent exhaustion that made it challenging to focus on work. Reluctant to seek medical attention, she eventually consulted a doctor after developing a persistent rash on her arm, a classic sign of celiac disease. The doctor suspected irritable bowel syndrome (IBS) but decided to conduct comprehensive blood tests, including one for celiac disease. Upon receiving a positive test result for the tTG IgA antibody, indicating her immune system's reaction to gluten ingestion, the young woman experienced a mix of relief and dread. While relieved to have an explanation for her symptoms, she struggled with the idea of giving up her favorite foods. A Strict Gluten-Free Diet for Life Her treatment journey involved consultations with a gastroenterologist and adhering to a strict gluten-free diet for life. This dietary overhaul meant not only eliminating obvious sources of gluten but also being vigilant about hidden sources in sauces and seasonings. Supported by a dietitian, she gradually adapted to her new lifestyle, learning to read labels, explore gluten-free recipes, and advocate for her dietary needs in social settings. Despite occasional challenges, she found empowerment in managing her condition and cherishing the support of her partner, who joined her in adopting a gluten-free diet. Today, she embraces her life with celiac disease, prioritizing her well-being and enjoying newfound vitality. Read more about Chelsea's story at msn.com

Celiac.com 03/04/2024 - Chugai Pharmaceutical Co., Ltd. has announced significant strides in the development of a potential treatment for celiac disease with their novel multi-specific antibody, DONQ52. The company recently announced that the non-clinical research results on DONQ52 have been published in Nature Communications, a prestigious multidisciplinary scientific journal. This milestone represents a significant step forward in the quest to find effective therapies for celiac disease, a condition currently without approved treatment options. DONQ52, discovered by Chugai, has shown promise in selectively inhibiting the immune response to gluten, a key component in the pathology of celiac disease. Through advanced antibody engineering technologies, DONQ52 was designed to target and neutralize multiple gluten peptides in complex with HLA-DQ2.5, a genetic marker strongly associated with celiac disease. The research findings published in Nature Communications outline the potential of DONQ52 to effectively inhibit gluten-dependent T-cell activation, a crucial step in the immune response cascade that leads to intestinal damage in celiac disease. Notably, DONQ52 demonstrated broad and selective recognition of over 25 distinct pathogenic gluten peptides, indicating its versatility and potential as a therapeutic agent. The Goal is to Develop a Therapy that can Provide Relief to Individuals Living with Celiac Disease Dr. Osamu Okuda, President and CEO of Chugai, expressed optimism about the future of DONQ52 in celiac disease treatment. He highlighted the ongoing Phase I clinical study, which aims to assess the safety and efficacy of DONQ52 in patients with celiac disease. The ultimate goal is to develop a therapy that can provide relief to individuals living with celiac disease, addressing an unmet medical need in the field. “We are very pleased to announce that that the results of basic research on a multi-specific antibody DONQ52 discovered by our company have been published in Nature Communications. Although technical hurdles have prevented practical use to date, our non-clinical study shows that specific and broad inhibition of HLA-T cell interactions is a useful therapeutical approach for celiac disease,” said Dr. Okuda. As the Phase I study progresses, Chugai remains committed to advancing the development of DONQ52 and leveraging their expertise in antibody engineering to explore new possibilities in celiac disease therapy. With continued research and innovation, DONQ52 has the potential to offer hope and improved quality of life for those affected by celiac disease. Stay tune for more on this and related stories. Read more at chugai-pharm.co.jp

Celiac.com 12/23/2023 - Celiac disease, an autoimmune condition triggered by gluten consumption, has seen remarkable progress in recent research endeavors. This article delves into the latest breakthroughs, ongoing clinical trials, and the prospective landscape of celiac disease treatments. From innovative therapies to promising drug developments, the aim is to unravel the potential impact of these advancements on the lives of individuals with celiac disease. Understanding Celiac Disease: A Brief Overview Celiac disease stands as a multifaceted autoimmune condition triggered by the consumption of gluten, a protein found in wheat, barley, and rye. With a prevalence reaching approximately 1% of the global population, this chronic disorder poses unique challenges to individuals whose immune systems react adversely to gluten ingestion. At its core, celiac disease is characterized by an abnormal immune response that targets the small intestine. Gluten consumption sets off an inflammatory reaction, leading to damage to the lining of the small intestine and impairing its ability to absorb nutrients. This often results in a range of symptoms, from gastrointestinal distress and malabsorption issues to fatigue, joint pain, and neurological complications. Diagnosis is a multifaceted process involving a combination of blood tests, genetic testing, and, often, confirmation through an intestinal biopsy. It's crucial to recognize that celiac disease can manifest in diverse ways, making diagnosis challenging and underscoring the importance of comprehensive medical evaluation. For those diagnosed with celiac disease, the primary and only effective treatment is strict adherence to a gluten-free diet. By eliminating gluten-containing foods, individuals can manage symptoms, allow the small intestine to heal, and prevent complications associated with ongoing inflammation. As we embark on the exploration of recent research advances, it is paramount to grasp the fundamental aspects of celiac disease. This understanding lays the groundwork for appreciating the significance of breakthroughs, clinical trials, and emerging treatments in the dynamic landscape of celiac disease research. Genetic Research and Personalized Medicine Genetic research has emerged as a cornerstone in unraveling the complexities of celiac disease. The strong genetic component of the condition is underscored by the association with specific human leukocyte antigen (HLA) genes, particularly the HLA-DQ2 and HLA-DQ8 variants. Individuals carrying these genetic markers are more predisposed to developing celiac disease when exposed to gluten. Advancements in genetic research not only enhance our understanding of celiac disease's hereditary nature but also pave the way for personalized medicine approaches. Genetic testing allows for the identification of at-risk individuals, enabling targeted screening and early intervention. This precision in diagnosis is pivotal, as it empowers healthcare providers to tailor their approach based on an individual's genetic predisposition, optimizing the efficacy of interventions and improving overall patient outcomes. Moreover, ongoing genetic research delves into the intricate interplay of various genetic factors that contribute to the diverse manifestations of celiac disease. Unraveling these genetic intricacies holds the promise of unveiling novel therapeutic targets and refining risk prediction models. The integration of genetic insights into the realm of personalized medicine marks a paradigm shift in celiac disease management, steering us towards more nuanced and individualized approaches to diagnosis, treatment, and long-term care. As genetic research continues to unfold, the potential for groundbreaking discoveries that shape the future of celiac disease care becomes increasingly apparent. Breakthrough Therapies on the Horizon The quest for innovative and effective therapies for celiac disease has ushered in a new era of research and development. Breakthroughs on the horizon promise transformative approaches that go beyond the conventional reliance on a gluten-free diet. These pioneering therapies aim to address the underlying immune response and inflammation characteristic of celiac disease, providing new avenues for individuals seeking relief and an improved quality of life. One notable breakthrough involves the exploration of enzyme therapies designed to break down gluten in the digestive system, rendering it less immunogenic. These enzymes, often referred to as glutenases, hold the potential to mitigate the impact of accidental gluten exposure and offer individuals with celiac disease a degree of dietary flexibility. Immunomodulatory therapies represent another frontier in celiac disease research. By targeting specific components of the immune system responsible for the aberrant response to gluten, these therapies aim to modulate immune activity and alleviate the inflammatory cascade triggered by gluten ingestion. These approaches hold promise in not only managing symptoms but also addressing the root cause of celiac disease. Additionally, advancements in the realm of nanotechnology and drug delivery systems contribute to the development of novel strategies for gluten detoxification. Nanoparticle-based approaches seek to encapsulate gluten, preventing its interaction with the immune system and reducing its harmful effects on the intestine. While these breakthrough therapies are in various stages of preclinical and clinical development, their potential to revolutionize celiac disease management is evident. As research progresses, the prospect of a more diversified therapeutic landscape offers hope to individuals with celiac disease, signaling a future where effective treatments extend beyond dietary restrictions. Clinical Trials: Navigating the Path to Approval Clinical trials stand at the forefront of translating scientific discoveries into tangible treatments for celiac disease. These rigorous investigations represent a critical phase in the development of new therapies, assessing their safety, efficacy, and overall impact on patient outcomes. Navigating the path to approval involves a systematic and regulated approach, encompassing various phases that rigorously evaluate the intervention's viability and potential benefits. The journey begins with Phase 1 trials, where the focus is primarily on the therapy's safety profile. Small groups of participants are enrolled, and the treatment's tolerability and potential side effects are closely monitored. Following successful Phase 1 outcomes, researchers progress to Phase 2 trials, expanding the participant pool to assess both safety and initial efficacy in a larger and more diverse cohort. Phase 3 trials constitute a pivotal stage, involving a more extensive participant population to provide robust data on the therapy's effectiveness, safety, and optimal dosage. These trials often employ a randomized and controlled design, comparing the investigational therapy against a placebo or standard treatment to ensure statistically significant results. Upon completion of successful Phase 3 trials, researchers compile comprehensive data for regulatory submissions seeking approval from health authorities. Regulatory agencies meticulously review the evidence to ascertain the therapy's safety and efficacy, with the potential for market approval if deemed beneficial and safe for patient use. Engaging in clinical trials requires collaboration between researchers, healthcare professionals, and individuals with celiac disease who voluntarily participate in these groundbreaking studies. Their contributions play a pivotal role in advancing the field, bringing us closer to a future where novel therapies offer renewed hope and improved outcomes for the celiac community. Innovative Drug Developments In the dynamic landscape of celiac disease research, innovative drug developments are catalysts for transformative change. The pursuit of novel pharmaceutical interventions goes beyond traditional dietary restrictions, offering a spectrum of therapeutic possibilities. These groundbreaking developments aim to address the intricate immunological and inflammatory processes at the core of celiac disease, providing hope for enhanced management and improved quality of life for those affected. Monoclonal antibodies represent a forefront in innovative drug development for celiac disease. These antibodies are designed to specifically target and neutralize key components of the immune response associated with gluten-induced inflammation. By modulating immune activity, monoclonal antibodies hold promise in mitigating the damaging effects of gluten ingestion and preventing the cascade of events leading to intestinal damage. Small molecule drugs tailored to interrupt specific pathways involved in the immune response to gluten also feature prominently in ongoing research. These compounds, often designed to be orally administered, aim to provide a systemic impact on celiac disease, offering an alternative to dietary restrictions. As these drugs progress through clinical trials, their potential to revolutionize the therapeutic landscape becomes increasingly apparent. The exploration of microbiome-based therapies adds an additional layer of innovation to celiac disease drug development. Leveraging the intricate relationship between gut microbes and the immune system, these therapies seek to restore balance and tolerance to gluten. Manipulating the microbiome holds promise in creating a more resilient and tolerant gut environment, potentially reducing the severity of celiac disease symptoms. While these innovative drug developments are in various stages of research and clinical testing, their emergence signifies a paradigm shift in how we approach celiac disease. By expanding the therapeutic toolkit, researchers aim to provide individuals with celiac disease options that align with their unique needs and contribute to a future where effective pharmaceutical interventions coexist with dietary management. The Role of Diet and Nutritional Therapies Diet remains a cornerstone in managing celiac disease, and ongoing research continues to refine nutritional strategies to optimize health outcomes for individuals with this autoimmune condition. Understanding the intricate relationship between diet and celiac disease is crucial for effective symptom management, promoting gut healing, and ensuring overall well-being. Gluten-Free Diet: A Necessity for Celiac Disease Management The foundation of celiac disease management lies in the strict adherence to a gluten-free diet. Eliminating gluten-containing grains such as wheat, barley, and rye is essential to prevent immune-mediated damage to the small intestine. A gluten-free diet requires vigilance in scrutinizing food labels, choosing naturally gluten-free foods, and adopting gluten-free cooking practices to avoid cross-contamination. Beyond Gluten: Exploring Nutritional Support While the removal of gluten is non-negotiable for those with celiac disease, attention to overall nutritional support is equally vital. Deficiencies in key nutrients such as iron, calcium, vitamin D, and B vitamins are common in individuals with celiac disease due to malabsorption issues. Nutritional therapies focus on addressing these deficiencies through dietary modifications, supplementation, and monitoring. Potential of Microbiome Modulation Recent research highlights the dynamic interplay between the gut microbiome and celiac disease. The composition of gut bacteria influences immune responses and may play a role in the development and progression of the disease. Exploring nutritional strategies to modulate the microbiome, such as probiotic supplementation and prebiotic-rich foods, holds promise in promoting gut health and optimizing the nutritional status of individuals with celiac disease. Personalized Nutrition: Tailoring Dietary Approaches Recognizing the diverse presentations of celiac disease, researchers delve into the realm of personalized nutrition. Tailoring dietary approaches to individual needs considers factors such as symptom severity, coexisting conditions, and nutritional requirements. Personalized nutrition aims to enhance dietary compliance, address specific nutritional deficiencies, and improve the overall quality of life for those managing celiac disease. As our understanding of the intricate relationship between diet and celiac disease evolves, nutritional therapies continue to play a pivotal role in comprehensive management strategies. Balancing the strict requirements of a gluten-free diet with personalized nutritional support contributes to the holistic care of individuals with celiac disease, fostering optimal health and well-being. Challenges and Considerations in Celiac Disease Research As the landscape of celiac disease research expands, researchers face various challenges and considerations that shape the trajectory of scientific inquiry and impact the translation of findings into tangible advancements for patients. Navigating these complexities is crucial for fostering progress, ensuring the validity of research outcomes, and addressing the multifaceted nature of celiac disease. Heterogeneity in Celiac Disease Presentations Celiac disease exhibits a diverse spectrum of clinical presentations, ranging from classic gastrointestinal symptoms to atypical or silent forms. This heterogeneity poses a challenge in both diagnosis and research, as individuals may present with varying degrees of symptom severity and associated conditions. Researchers grapple with the need to account for this diversity in study cohorts, considering the implications for generalizability and personalized treatment approaches. Diagnostic Limitations and Evolving Criteria Accurate diagnosis is fundamental to celiac disease research, yet diagnostic criteria and tools continue to evolve. Serological tests, histological analysis, and genetic markers contribute to diagnosis, but challenges persist in cases of seronegative celiac disease and potential overlap with other gastrointestinal conditions. Researchers must navigate the nuances of diagnostic criteria, considering advancements and potential limitations in standardizing assessments across studies. Long-Term Implications and Outcomes Understanding the long-term implications of celiac disease, including its impact on quality of life, comorbidities, and associated complications, requires longitudinal research. Tracking outcomes over extended periods presents logistical challenges, including participant retention, data accuracy, and the dynamic nature of patient experiences. Longitudinal studies are essential for unraveling the multifaceted nature of celiac disease progression and its consequences. Interplay of Genetics, Environment, and Microbiome Celiac disease's etiology involves a complex interplay of genetic predisposition, environmental factors, and the gut microbiome. Untangling these interconnected elements presents a formidable challenge, as researchers strive to elucidate the role of specific genes, environmental triggers, and microbiome dynamics in disease onset and progression. Collaborative and interdisciplinary approaches are essential for comprehensively addressing these multifactorial influences. Translation of Research Findings into Clinical Practice Bridging the gap between research findings and clinical practice is a critical consideration in celiac disease research. Successful translation requires effective communication between researchers, healthcare providers, and individuals with celiac disease. Implementing evidence-based recommendations, disseminating research outcomes to diverse stakeholders, and fostering awareness are integral aspects of ensuring that advancements in research positively impact patient care. Addressing these challenges and considerations requires ongoing collaboration, innovation, and a commitment to advancing our understanding of celiac disease. As research endeavors continue, the collective efforts of the scientific community play a pivotal role in overcoming obstacles, refining diagnostic and therapeutic approaches, and ultimately improving outcomes for individuals living with celiac disease. Patient Perspectives: Voices from the Celiac Community In the realm of celiac disease research, the voices and experiences of individuals living with the condition provide invaluable insights that complement scientific findings. Patient perspectives offer a nuanced understanding of the challenges, triumphs, and day-to-day realities faced by those navigating life with celiac disease. These firsthand accounts contribute to the broader dialogue surrounding the condition and enrich both research initiatives and the broader celiac community. Navigating Diagnosis and Treatment Journeys Patients with celiac disease often encounter a labyrinthine journey in obtaining an accurate diagnosis and navigating subsequent treatment paths. Sharing personal stories illuminates the diverse pathways individuals take in seeking answers to their health concerns, from initial symptoms to the diagnostic process and the subsequent initiation of a gluten-free lifestyle. These narratives underscore the need for improved awareness, timely diagnosis, and accessible support networks. Quality of Life and Daily Challenges Understanding the impact of celiac disease on individuals' quality of life requires an exploration of the daily challenges they face. Patient perspectives shed light on the intricacies of managing a gluten-free diet, coping with social and emotional aspects, and addressing the broader implications of the condition on mental and physical well-being. Capturing these nuanced experiences informs research priorities, emphasizing the holistic needs of individuals with celiac disease. Advocacy and Community Engagement The celiac community is characterized by a strong spirit of advocacy and mutual support. Patient perspectives highlight the role of individuals in advocating for improved awareness, research funding, and policy changes that benefit the broader community. Engaging with patient advocacy groups, sharing success stories, and mobilizing collective efforts amplify the impact of patient voices in shaping the trajectory of celiac disease research and fostering a sense of community. Challenges and Triumphs in Gluten-Free Living Living gluten-free entails a myriad of challenges, from navigating restaurant menus to deciphering food labels and managing potential cross-contamination risks. Patient narratives capture the triumphs and tribulations of gluten-free living, offering practical insights into coping strategies, favorite recipes, and innovative approaches to enhancing the gluten-free lifestyle. These stories resonate with others facing similar challenges and provide a platform for shared learning and support. Collaboration Between Patients and Researchers The synergy between patients and researchers is integral to advancing celiac disease research. Patient perspectives contribute to research prioritization, study design, and the development of patient-centered outcomes. Collaborative initiatives that involve individuals with celiac disease in research endeavors foster a sense of shared ownership and promote research that is reflective of the diverse needs and experiences within the community. In amplifying the voices of the celiac community, patient perspectives serve as a powerful catalyst for positive change. By integrating these narratives into the fabric of celiac disease research, we honor the lived experiences of individuals, foster a more empathetic and informed approach to patient care, and collectively work towards a future where the journey with celiac disease is understood, supported, and empowered. The Future Landscape of Celiac Disease Treatment As the field of celiac disease research advances, the prospect of innovative and targeted treatments heralds a transformative era for individuals living with the condition. The future landscape of celiac disease treatment holds promise, with ongoing research endeavors exploring novel therapeutic avenues and potential interventions. This section delves into the evolving landscape of celiac disease treatment, highlighting key areas of exploration and envisioning the potential trajectory of future interventions. Immunomodulatory Therapies Immunomodulatory therapies represent a forefront area of investigation in celiac disease treatment. Researchers are exploring strategies aimed at modulating the immune response to gluten, thereby mitigating the inflammatory cascade that characterizes the condition. From targeted immunotherapies to interventions that induce gluten tolerance, the goal is to develop treatments that allow individuals with celiac disease greater dietary flexibility while maintaining immune balance. Enzyme Therapies and Gluten Digestion Enzyme therapies designed to enhance gluten digestion are emerging as a potential avenue for celiac disease management. These therapies involve the use of enzymes that break down gluten into non-immunogenic fragments, reducing the likelihood of triggering an immune response. While challenges exist in achieving complete gluten degradation, ongoing research explores the feasibility and safety of enzyme-based approaches as adjuncts to a gluten-free diet. Microbiome Modulation The gut microbiome's intricate role in celiac disease pathogenesis has sparked interest in microbiome modulation as a potential therapeutic strategy. Research aims to understand how specific microbial compositions influence gluten metabolism and immune responses. Modulating the microbiome through probiotics, prebiotics, or fecal microbiota transplantation represents a novel frontier in addressing the dysbiosis associated with celiac disease and fostering a gut environment conducive to tolerance. Personalized and Precision Medicine Advancements in personalized and precision medicine offer a tailored approach to celiac disease treatment. Genetic profiling, biomarker identification, and individualized treatment plans based on specific patient characteristics are integral components of this evolving paradigm. Tailoring interventions to address the heterogeneity of celiac disease presentations enhances treatment efficacy and aligns with the broader trend toward precision medicine in autoimmune conditions. Therapeutic Vaccines Therapeutic vaccines designed to induce immune tolerance to gluten are under investigation as potential interventions for celiac disease. These vaccines aim to reprogram the immune system's response to gluten, allowing individuals to consume gluten-containing foods without triggering an adverse reaction. While challenges related to vaccine design and long-term efficacy persist, ongoing research holds promise for a future where therapeutic vaccines become a viable treatment option. Patient-Centered Approaches and Shared Decision-Making The future landscape of celiac disease treatment emphasizes patient-centered approaches that prioritize individual preferences, values, and goals. Shared decision-making between healthcare providers and individuals with celiac disease becomes paramount in tailoring treatment plans to align with patients' lifestyle, dietary choices, and overall well-being. Empowering individuals with information and involving them in treatment decisions fosters a collaborative and patient-centric care model. While these potential avenues offer glimpses into the future of celiac disease treatment, ongoing research, clinical trials, and collaborative efforts will determine the feasibility, safety, and efficacy of these interventions. As the scientific community continues to unravel the complexities of celiac disease, the prospect of transformative treatments brings hope for enhanced quality of life and improved management strategies for individuals living with this autoimmune condition. Conclusion In navigating the intricate terrain of celiac disease research, this exploration reveals a landscape marked by significant strides, promising breakthroughs, and a collective commitment to transforming the lives of individuals affected by gluten intolerance. From the realms of genetic insights guiding personalized medicine to the forefront of innovative therapies and ongoing clinical trials, the journey towards effective celiac disease treatment is unfolding. As we envisage the future, a convergence of multidisciplinary approaches, patient-centered care, and cutting-edge pharmaceutical developments emerges. The synergy of researchers, healthcare professionals, and the resilient celiac community propels us towards a horizon where the burdens of celiac disease are lightened, and individuals can embrace a life unrestricted by the constraints of gluten intolerance. Yet, this journey is not without its challenges. Regulatory intricacies, the need for increased research funding, and the imperative for sustained patient advocacy underscore the complexity of the path ahead. In the face of these challenges, however, the resilience and determination witnessed in the celiac community serve as a beacon of hope, propelling research forward and fostering an environment where breakthroughs become a reality. The evolving narrative of celiac disease research paints a picture of optimism, collaboration, and a shared vision for a future where effective treatments abound. As we reflect on the progress made and anticipate what lies ahead, let us remain steadfast in our pursuit of alleviating the impact of celiac disease and championing a future where individuals can thrive without the constraints of gluten intolerance. Together, we stride towards a horizon where the promises of research translate into tangible improvements in the lives of those navigating the challenges of celiac disease. Further reading: Celiac Disease Foundation - Celiac Disease Foundation Research National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - Celiac Disease Research at NIDDK Clinical Trials Beyond Celiac - Research and Innovation Gluten Intolerance Group - Research and Education American College of Gastroenterology (ACG) - Celiac Disease Overview PubMed - Celiac Disease Research Articles

Celiac.com 12/21/2023 - Celiac Disease is a chronic intestinal condition affecting over 1% of the global population, and has long been treated with a gluten-free diet. However, limitations in efficacy and challenges for certain patient groups have spurred research into alternative treatments. A team of researchers recently set out to explore emerging pharmacological approaches for celiac disease, considering tolerance induction strategies, tissue transglutaminase (TG2) inhibition, gluten degradation, and interleukin (IL)-15 inhibition. The research team included Tessa Dieckman, Frits Koning, and Gerd Bouma. They are variously affiliated with the Department of Gastroenterology and Hepatology, Amsterdam UMC, location VU Medical Center, AGEM Research Institute, Amsterdam, the Netherlands, and the Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands. While a gluten-free diet remains safe and effective for most celiac disease patients, the study underscores the need for novel treatments that offer at least comparable efficacy and safety, considering potential higher costs associated with pharmacological options. The Review Highlights the Ongoing Investigation of Various Treatment Modalities Tolerance Induction: Nanoparticles loaded with gluten extract (TAK-101) show promise by inducing tolerance and decreasing gluten-induced mucosal injury. TG2 Inhibition: Inhibiting TG2 is another avenue of interest, potentially affecting gluten-induced mucosal injury. PRV-015 (AMG 714) and the anti-gliadin antibody (AGY) are under scrutiny, demonstrating efficacy in improving clinical symptoms. Enzyme Therapy: TAK-062, an enzyme therapy, exhibits efficient gluten degradation in vivo, a crucial aspect for preventing gluten-specific CD4 T cell responses in the small intestine. While drugs like TAK-101 and TG2 inhibitors reveal promise in decreasing mucosal injury, others, such as PRV-015 and AGY, exhibit efficacy in symptom improvement. Enzyme therapy, represented by TAK-062, holds potential for degrading gluten effectively, with applications either as an adjunct to a gluten-free diet or in preventing symptoms due to gluten contamination. The review emphasizes the diversity in immunological and clinical responses among celiac disease patients to varying gluten amounts, necessitating further investigation. In conclusion, the active research in novel celiac disease treatment modalities holds promise for unmet patient needs. However, questions regarding efficacy and safety endpoints must be addressed before these treatments can be integrated into standard celiac disease care. Until then, the gluten-free diet remains the primary treatment for celiac disease. Read more in Sciencedirect.com

Celiac.com 12/13/2023 - Celiac disease is a common autoimmune disease affecting more than 1% of the population. In celiac disease, the ingestion of gluten, a protein found in wheat, barley, and rye, triggers an immune response targeting the small bowel. In susceptible individuals, this immune reaction leads to both gastrointestinal and systemic symptoms. Unlike some other autoimmune diseases, the specific immunogenic antigens responsible for the immune response in celiac disease have been identified and extensively characterized. Consequently, a gluten-free diet has long been established as an effective treatment. This is not an easy task, partly due to a lack of awareness of the gluten content in foods, and the extensive incorporation of gluten into many processed foods. Furthermore, a gluten-free diet can impose a sense of limitation, and can be associated with decreased quality of life, in some celiac disease patients. This contributes to gluten contamination in the diets of four out of five celiacs trying to follow a gluten-free diet. Furthermore, one in three adult celiac patients will report persistent symptoms, while two in three will not achieve full histological recovery when on a gluten-free diet. In recent years, extensive research has fueled a quest for a pharmacological treatment for celiac disease, the development of which represents a sort of a Holy Grail for many researchers and patients. A new review presents a concise description of the current rationale and main clinical trials related to celiac disease drug therapy. The review is the work of by Professor Mariana Verdelho Machado, with the Gastroenterology Department, Hospital de Vila Franca de Xira, Nª 2, Vila Franca de Xira, Portugal; and the Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, Lisbon, Portugal. Estimates suggest that over 1% of the global population, roughly 80 million people, is affected by celiac disease. The classical presentation involves symptoms of malabsorption, such as diarrhea, weight loss, and nutritional deficits. However, a significant portion of patients either remains asymptomatic or experiences non-specific and extra-intestinal symptoms. Despite the challenges posed by the strict dietary regimen, achieving mucosal healing through a gluten-free diet is crucial, particularly given the increased mortality observed in some cohorts of celiac patients. Challenges with the Gluten-Free Diet The gluten-free diet is currently the only proven effective treatment for celiac disease. However, its implementation presents various challenges. Adherence rates to a strict gluten-free diet fluctuate widely, ranging from 42% to 91%. Moreover, even among those who claim adherence, up to 80% might inadvertently consume gluten due to contamination or non-compliance. Additionally, achieving mucosal healing, a critical aspect of managing celiac disease, appears to occur in less than half of adults following a gluten-free diet. Rationale for Drug Development In the past decade, there has been a concerted effort to explore pharmacological treatments for celiac disease. The endeavor is particularly challenging as a well-established, non-pharmacological therapy— the gluten-free diet—already exists. For a new drug to be a viable alternative, it must demonstrate efficacy, lack significant adverse effects, be simple to administer (preferably orally), and be cost-effective. Pharmacological Treatments in Focus Efforts in drug development for celiac disease have focused on three main scenarios: maintenance therapy, rescue therapy after acute gluten exposure, and mitigation of chronic inadvertent gluten exposure. Larazotide: One drug in clinical research is larazotide, designed to stabilize enterocyte tight junctions, thereby reducing intestinal permeability. While phase 2 studies showed promising results in decreasing symptoms and serological markers, a phase 3 trial in 2022 was suspended after an interim analysis revealed no meaningful effects. Latiglutenase: Another promising drug is latiglutenase, a mix of glutenases. Phase 2 studies demonstrated its efficacy in preventing mucosal degradation and symptom development resulting from gluten contamination. Latiglutenase is considered a strong candidate for becoming a standard adjunctive therapy in celiac disease treatment. IL-15 Pathway Inhibition: For patients unresponsive to a gluten-free diet or those with refractory celiac disease (RCD), research has focused on the IL-15 pathway. While blocking IL-15 with PRN15 showed disappointing results, tofacitinib, a pan-JAK inhibitor acting on the IL-15 receptor signaling pathway, appears promising. Immune Tolerance Induction: Inducing immune tolerance to gluten is an appealing strategy to avoid systemic immune suppression. Strategies like therapeutic vaccines and hookworm infestation, despite initial disappointment, have not been entirely ruled out. Future Prospects and Considerations The ongoing research prompts questions about the role these emerging drugs might play in treating extra-intestinal manifestations associated with celiac disease, such as neuropsychiatric and autoimmune conditions. While these drugs offer hope, they must surpass the effectiveness and safety of the existing dietary therapy, a high bar given the complexity of celiac disease and the challenges posed by gluten exposure. The researchers conclude that celiac disease patients need effective and practical treatment options beyond the stringent gluten-free diet. They also note that ongoing developments in pharmacological treatments bring hope for improved management, especially for patients facing challenges with dietary adherence and inadvertent gluten exposure. However, the complexity of celiac disease demands a meticulous approach to drug development, ensuring not only efficacy and ease of use, but also safety and accessibility. As research progresses, the landscape of celiac disease management may witness transformative changes, offering a brighter outlook for those living with this autoimmune condition. Read more in the Int. J. Mol. Sci. 2023, 24(2), 945.

Celiac.com 11/15/2023 - Imagine enjoying your favorite pasta dish one day, and the next day, experiencing mysterious and uncomfortable symptoms like stomach pain, vomiting, fatigue, or skin rashes. What could be causing these problems? One possibility might be celiac disease. Celiac disease is a relatively common autoimmune disorder that affects the small intestine. It's triggered by the consumption of gluten, a protein found in wheat, barley, and rye. When someone with celiac disease eats gluten, their immune system reacts by damaging the lining of the small intestine, which can lead to a wide range of symptoms and complications. Getting the diagnosis correct is important, because celiac disease is often misdiagnosed. Symptoms of Celiac Disease The symptoms of celiac disease can vary greatly from person to person, and some individuals may not experience any symptoms at all. Here are some common signs to watch out for: Digestive Troubles: Symptoms often involve the digestive system, such as diarrhea, constipation, bloating, gas, and abdominal pain. Fatigue: Many people with celiac disease report feeling excessively tired, even after a full night's sleep. Weight Loss: Unintended weight loss can occur due to malabsorption of nutrients caused by intestinal damage. Skin Issues: Some individuals develop skin conditions, itchy rashes, like dermatitis herpetiformis, which is closely linked to celiac disease. Joint Pain: Joint pain and inflammation may affect those with celiac disease. Mood Changes: Mood swings, depression, or anxiety can be related to the condition. Delayed Growth in Children: Celiac disease can hinder proper growth and development in children. Diagnosis of Celiac Disease Getting a proper diagnosis is crucial for managing celiac disease effectively. Here's how doctors typically diagnose it: Blood Tests: Initially, blood tests are done to check for elevated levels of certain antibodies, such as anti-tissue transglutaminase (tTG) and anti-endomysial antibodies (EMA). Higher levels of these antibodies can be a sign of celiac disease. Biopsy: If blood tests indicate celiac disease, a small intestine biopsy may be performed. During this procedure, a tiny sample of the intestinal lining is taken and examined under a microscope. Damage to the lining is a key indicator of the disease. In more and more cases, celiac disease can be diagnosed without biopsy. Treatment of Celiac Disease The primary treatment for celiac disease is a strict gluten-free diet. Once diagnosed, individuals need to eliminate all sources of gluten from their diet, including bread, pasta, cakes, and even certain sauces. This can be challenging, as gluten can hide in unexpected places, so reading food labels and avoiding gluten ingredients is a must. Most people with celiac disease notice significant improvements in their symptoms once they adopt a gluten-free lifestyle. Over time, the intestinal lining often heals, allowing for better nutrient absorption. In some cases, complications of celiac disease may require additional medical attention. For instance, individuals with severe malabsorption may need vitamin and mineral supplements. Dermatitis herpetiformis may be treated with medications. Living with Celiac Disease While a gluten-free diet is the cornerstone of managing celiac disease, it's also essential to be vigilant about cross-contamination. This means avoiding utensils, kitchen appliances, and cooking surfaces that have come into contact with gluten-containing foods. Celiac.com offers numerous forums for discussing celiac disease and gluten-free challenges with other celiacs who can share experience and help guide your celiac and gluten-free journey. Support groups and dietary counselors can be incredibly helpful for those newly diagnosed with celiac disease. They provide practical tips for maintaining a gluten-free lifestyle and offer emotional support during the transition. In conclusion, celiac disease is a common but manageable condition. By recognizing its symptoms, seeking a proper diagnosis, and committing to a gluten-free diet, individuals with celiac disease can lead healthy and fulfilling lives. If you suspect you have celiac disease, don't hesitate to consult a healthcare professional for guidance and testing. Your well-being is worth it!

Celiac.com 10/06/2023 - Typically, treating autoimmune diseases involves broad immunosuppression, which has various side effects. However, a team of researchers have developed a novel approach to suppress established antigen-specific immune responses without the need for global immunosuppression. The research team includes Andrew C. Tremain, Rachel P. Wallace, Kristen M. Lorentz, Thomas B. Thornley, Jennifer T. Antane, Michal R. Raczy, Joseph W. Reda, Aaron T. Alpar, Anna J. Slezak, Elyse A. Watkins, Chitavi D. Maulloo, Erica Budina, Ani Solanki, Mindy Nguyen, David J. Bischoff, Jamie L. Harrington, Rabinarayan Mishra, Gregory P. Conley, Romain Marlin, Nathalie Dereuddre-Bosquet, Anne-Sophie Gallouët, Roger LeGrand, D. Scott Wilson, Stephan Kontos, and Jeffrey A. Hubbell. They are variously affiliated with the Committee on Immunology, University of Chicago, Chicago, IL, USA; the Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA; the Committee on Cancer Biology, University of Chicago, Chicago, IL, USA; the Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; the Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France; the Animal Resources Center, University of Chicago, Chicago, IL, USA; and with Anokion US Inc., Cambridge, MA, USA. Their study introduces a new method using a polymer glycosylated with N-acetylgalactosamine (pGal) that is conjugated to the antigen. This approach enables the dissociation of the antigen upon endocytosis, allowing it to be presented in an immunoregulatory environment. The research demonstrates that pGal–antigen therapy can induce antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis, driven by the programmed cell-death-1 pathway and the co-inhibitory ligand CD276. Moreover, this therapy effectively suppresses antigen-specific responses in non-human primates vaccinated against a DNA-based simian immunodeficiency virus. In essence, pGal–antigen therapy offers a promising avenue for addressing autoimmune diseases by specifically targeting and resolving antigen-specific inflammatory T-cell responses. In the future, this approach could be applied to various autoimmune diseases, possibly even celiac disease, offering a more precise and effective alternative to current treatments that rely on broader immunosuppression. Read more in Nature Biomedical Engineering

Celiac.com 06/10/2023 - If you suffer from celiac disease like I do you are well aware that the current and only treatment recommended for the disease is a lifelong adherence to a strict gluten-free diet. Anyone who has tried a gluten-free diet knows that it works fine as a treatment for the disease, but it also can be difficult to deal with, especially when cooking, dining out, and buying food (it can also be expensive!). According to one line of research done over the past few years, however, there may be hope that one day in the not too distant future we might be able to eat gluten without harm. How—you ask? Immunotherapy In 2001 the Scandinavian Journal of Immunology published an article authored by a group of Italian scientists wherein mice were used to test a new idea called immunomodulation and its ability to treat celiac disease. The scientists purified the protein gliadin (the component of gluten that triggers immune-mediated injury when ingested by people with celiac disease), fractionated it, and then administered the different fragments intra-nasally to laboratory mice (presumably transgenic mice with induced celiac disease, although this is unclear) and noted the results. They found that when a particular fragment of gliadin, which they refer to as alpha-gliadin, was administered intra-nasally it down-regulated T-cell proliferation and interferon-gamma production in response to whole gliadin in vitro. This lead the scientists to make the statement that "these results demonstrate how an immune response to a complex antigen may be controlled by treatment with a purified component and specifically indicate alpha-gliadin to be a good candidate for further identification of short peptides to be used as tolerogens in this model(1)." Although immunomodulation sounds similar to allergy therapy it is not the same since the cells involved are different, as well as the method of induced tolerance. In therapy for allergic reactions tolerance is induced through injections, and the aim is to reduce histamine release, systemic anaphylactic responses, and even severe rhinitis. In immunomodulation the antigen in question is cleaved into smaller antigens, and the mixture of epitopes are used to induce tolerance via mucosal surfaces (i.e., the nose, parts of the respiratory tract, and the alimentary tract, to name a few). From my understanding, these are markedly different approaches, and the mucosal therapy appears to potentially be much more powerful and more selective in immune-suppression resulting ultimately in tolerance to the antigen. It is my hope that this research indicates a new avenue for the treatment of celiac disease, one which may be very soon in coming—possibly within the next decade. Of course, questions arise as to what exactly this particular experiment means, since findings were in vitro (i.e., test tube only, not within the body), were done on mice (murine studies), and do not seem to have been duplicated in humans at this point, suggesting difficulties / logistical problems with the protocol as it exists— using alpha-gliadin as a tolerogen to suppress immune response to dietary gliadin. Nonetheless, at the very least, this research signals that research advances are still being made into the understanding and treatment of celiac disease, and that better therapies and possibly even a cure for this disease may be on the horizon. Reference: Maurano F, Siciliano RA, De Giulio B, Luongo D, Mazzeo MF, Troncone R, Auricchio S, Rossi M. Intranasal administration of one alpha gliadin can downregulate the immune response to whole gliadin in mice. Scand J Immunol 2001 Mar;53(3): 290-5. Istituto di Scienze dell'Alimentazione, CNR, Via Roma 52, 83100 Avellino, Italy.

Celiac.com 08/17/2023 - KAN-101, the most recent drug designed to induce immune tolerance to wheat gluten, has proven safe and tolerable in the Phase 1 stage of testing. Now the hard work starts. The drug has shown promise for treating celiac disease, an autoimmune condition where the body reacts negatively to gluten in the small intestines. The drug, developed by Anokion, targets the liver to promote immune tolerance to gluten in people with celiac disease. KAN-101 Demonstrated Safety and Pharmacokinetic Potential In the first-in-human phase 1 ACeD trial, KAN-101 demonstrated safety and pharmacokinetic potential. The trial involved 41 adult patients with biopsy-confirmed celiac disease, all with the HLA-DQ2.5 genotype, which is associated with celiac disease. The patients received different doses of KAN-101 through intravenous administration. No Serious Adverse Events or Dose-limiting Toxicities Results showed that the drug had acceptable safety, with no serious adverse events or dose-limiting toxicities. Common mild to moderate side effects included nausea, diarrhea, abdominal pain, and vomiting, which were consistent with celiac disease symptoms. KAN-101 rapidly cleared from the patients' systems within approximately 6 hours, and there was no accumulation on repeated dosing. Deborah Geraghty, CEO of Anokion, expressed excitement about the drug's potential to induce immune tolerance to gluten, providing a durable treatment effect for celiac disease patients. With celiac disease currently lacking an FDA-approved treatment option, KAN-101 could be a game-changer. The research team plans to further analyze KAN-101's efficacy and safety in human patients, particularly with biomarker responses from a gluten challenge, at doses of 0.6 mg/kg or higher in those with celiac disease. If successful, KAN-101 could significantly impact the lives of those with celiac disease by providing a viable and effective treatment option. While the early testing is encouraging, it's a long haul from Phase 1 to full approval, and so far, no drug designed to treat celiac disease has made the journey. The failures are legion. So, celiac sufferers should take this news with a grain of salt. Read more at HCPlive.com

Celiac.com 06/14/2023 - Researchers from Lanzhou University in China, in collaboration with international scientists, say they have developed a promising new method for treating celiac disease. Led by Aman Khan, a Pakistani postdoctoral fellow at Lanzhou University, the team focused on isolating probiotic bacterial strains from Pakistani fermented sourdough bread to prevent the occurrence of celiac disease. Celiac disease is an immune disorder triggered by gluten consumption and is particularly prevalent in Asian countries like Pakistan, where diets high in gluten-containing foods are common. Khan aimed to leverage his expertise to aid those affected by this condition. Inspired by a previous study that isolated a probiotic strain from a traditional Chinese fermented food called jiangshui, which showed the ability to degrade uric acid and regulate gut microbiota, Khan and his team sought to isolate beneficial strains from Pakistani fermented sourdough bread. They successfully extracted probiotic bacterial strains called LZU-GM and conducted experiments on mice. Probiotics from Fermented Sourdough The results of their experiments and integrative analysis indicated that LZU-GM could mitigate the adverse effects of gluten additives in food and restore balance to gut microbiota in mice. However, further clinical trials are required to evaluate the safety and efficacy of these probiotics from fermented sourdough bread as a potential treatment for celiac disease. The team plans to continue their research by creating yogurt using the LZU-GM strains isolated from Pakistani sourdough bread and conducting additional experiments. Their goal is to develop a therapeutic adjunct agent that can be used in conjunction with existing treatments for celiac disease. The researchers believe their innovative solution holds promise for individuals living with this autoimmune disorder. Big Claims But Few Details While the researchers claim to have developed a promising new method for treating celiac disease, it is important to approach their findings with caution. The study focused on isolating probiotic bacterial strains from Pakistani fermented sourdough bread, aiming to prevent the occurrence of celiac disease. The results of experiments conducted on mice showed potential benefits, including the mitigation of adverse effects of gluten additives and restoration of gut microbiota balance. However, it is crucial to note that these findings are based on animal studies, and further clinical trials are necessary to assess the safety and efficacy of these probiotics in treating celiac disease in humans. More Evidence Needed Big claims require robust evidence, and at this stage, the evidence supporting the use of probiotic strains from fermented sourdough bread as a treatment for celiac disease is limited. While the preliminary results sound promising, it is important to emphasize the need for rigorous scientific investigation, including well-designed clinical trials, to validate the potential of these probiotics. Until conclusive evidence emerges from rigorous clinical trials, it is essential to remain cautious and prioritize thorough scientific scrutiny before considering these probiotics as a viable treatment option for individuals living with celiac disease. Read more in chinadaily.com

Celiac.com 05/15/2023 - Biotechnology company Immunic, Inc., focuses on developing oral, small molecule therapies for chronic inflammatory and autoimmune diseases, including celiac disease. Celiac disease is an autoimmune disorder that affects approximately 1% of people globally. People with celiac disease have an abnormal immune response to gluten, a protein found in wheat, barley, and rye. This abnormal immune response damages the lining of the small intestine, leading to malabsorption and other serious complications. The company recently announced positive results from the Part C portion of its Phase 1 clinical trial of IMU-856 in treating patients with celiac disease. The trial consisted of 36 patients with celiac disease who were randomized to receive placebo or one of two doses of IMU-856 (80 mg or 160 mg) for four weeks, followed by two weeks of gluten challenge. The trial assessed the protection of gut architecture, reduction of gluten-induced intestinal damage, improvement of patients' symptoms related to gluten exposure, dose-dependent changes in biomarker responses, and enhancement of nutrient absorption. The trial results showed that patients treated with IMU-856 had a dose-dependent reduction in gluten-induced damage to their intestinal villi, the small, finger-like projections in the small intestine that play a key role in nutrient absorption. The results also showed that IMU-856 restored the absorption of essential nutrients, such as vitamin B12, for red blood cell formation and the functioning of the brain and nervous system. Immunic believes the clinical evidence supports IMU-856's ability to re-establish proper gut cell renewal, which could prove useful in treating other gastrointestinal diseases. Patients treated with IMU-856 also saw improvement in disease-related symptoms such as bloating and tiredness, and the treatment was observed to be safe and well-tolerated. IMU-856's ability to re-establish proper gut cell renewal, observed in preclinical studies, translates into clinical benefits for patients with celiac disease. Most importantly, the observed protection of intestinal villi from gluten-induced damage, independent of celiac-specific targeting immune mechanisms, seems to be unique among proposed therapeutic approaches, and may be applicable to other gastrointestinal diseases. Immunic is now preparing for clinical phase 2b testing of IMU-856 in ongoing active celiac disease, while also considering other potential clinical applications for this first-in-class and orally available molecule. The positive results from the Phase 1 clinical trial of IMU-856 offer some hope for the development of a new therapeutic approach to treating celiac disease and other gastrointestinal disorders. The trial's success represents a significant milestone in the effort to develop safe and effective treatments for patients with celiac disease, and other chronic inflammatory and autoimmune conditions. The company believes that this data set provides initial clinical proof-of-concept for a new therapeutic approach to gastrointestinal disorders by promoting the regeneration of bowel architecture. Now, the story of a promising new celiac drug treatment is a story familiar to many of us. So far, the story has always ended the same way: the promising drug fails in the end. Here's hoping this one ends more happily. Stay tuned for more on this and related stories.

Celiac.com 06/17/2023 - A team at The Royal Melbourne Hospital in Australia is seeking people with celiac disease to test a new product which is potentially capable of rendering gluten innocuous to the lining of the small intestine in celiacs. FOLLOWING a life long research career studying gluten and its damaging effects in celiac patients, Professor Hugh Cornell, recently retired from the RMIT University, has developed an enzyme extract derived from pig intestine which is potentially capable of rendering gluten innocuous to the lining of the small intestine of celiac patients. The product, called 'Glutazyme' is now ready for clinical trial. A team at The Royal Melbourne Hospital is seeking people with celiac disease to test the product in a carefully conducted trial. 'Glutazyme' was developed on the basis of the theory that celiac patients lack an enzyme in the intestine which when present in normal people, is capable of fully digesting gluten. When intestinal enzyme extracts from celiac patients are added to gluten in the test tube, gluten is incompletely digested, leaving gluten fragments that are toxic to the lining of the small intestine. These semi-digested fragments produce flattening of the villi (finger like projections essential for proper absorption of nutrients) and quite a striking immunological reaction in the bowel, both of which are characteristic findings on biopsy specimens from celiac patients consuming a normal, gluten-containing diet However, added gluten does not damage the lining cells in the presence of the enzyme extract, compared in the same test tube system to gluten without the enzyme, when damage occurs. In addition, when a group of celiac patients were given a small dose of gluten together with the enzyme extract, fewer symptoms (diarrhea, bloating, pain) developed compared to what occurred in the same subjects challenged with gluten but not protected with the enzyme extract. Professor Cornell supported his research by characterizing which sequences of amino acids in gluten actually cause the damage in the test tube studies, and showed that these sequences are digested to simpler peptides (short sequences of amino acids) by enzymes present in the extract. Then he showed that these simple peptides were harmless to the intestine of celiac patients in his experimental test tube studies. These peptide sequences are present in wheat, barley and rye - all cereals well known to cause damage in celiac patients. A research consortium has been established which also includes Dr. Ted Stelmasiak (a biopharmaceutical expert), Professor Finlay Macrae from the Department of Gastroenterology and Head of Colorectal Medicine and Genetics at The Royal Melbourne Hospital, and Dr. Bob Anderson from the Walter and Eliza Hall Institute and Department of Gastroenterology, RMH. The team is now ready to further evaluate the product in celiac patients. The research is pitched at testing the product's ability to protect celiac patients from the damaging effects of small amounts of gluten in the diet. At present, it is foreseen that the product might be an adjunct to a gluten free diet, to help celiac patients who are sensitive to trace amounts of gluten, and to protect celiac patients from the effects of gluten introduced by accident, such as can occur while eating away from home. Potentially, the product might add immeasurably to the quality of life of celiac patients and reduce the nutritional consequences and complications of inadvertent exposure to gluten, but carefully controlled trials are needed to be sure of the efficacy of the product. It is essential that the product is thoroughly assessed: hence the trial will involve not only evaluating symptoms and their suppression by the enzyme extract, but also measure transglutaminase antibodies (one of the specific blood tests used to diagnose, and assess dietary compliance in, celiac patients). A smaller group of the participants will also undergo gastroscopy and small bowel biopsy before and after the gluten challenges (with and without the extract), so as to be quite sure that the product is capable of preventing any of the intestinal immune reactions typically seen in celiac patients on gluten-containing diets. By the nature of the research process which addresses the barriers of knowledge, there may of course be a null (no benefit) result. Some symptoms are likely to occur especially in the low gluten challenge (control) period when subjects are asked to add a small amount of gluten without the 'Glutazyme'. However, no long term consequences are expected from such a short challenge. Glutazyme itself is considered nontoxic and harmless. Professor Macrae is keen to interview any biopsy-proven celiac patients in Victoria, Australia who may be interested in participating in the research. The research is clearly dependent upon sufficient interest in the celiac community, and is of course ultimately for the benefit of celiac patients in general. Potential participants are encouraged to discuss the project with their doctor. The project will be approved by The Royal Melbourne Hospital Clinical Research and Ethics Committee before its anticipated commencement date in June. It will be conducted through the Celiac Clinic at The Royal Melbourne Hospital. This article first appeared in the Australian Coeliac newsletter, and is reprinted here by permission of the Australian Coeliac Society.

Celiac.com 06/03/2023 - This article first appeared in the Australian Coeliac newsletter, and is reprinted here by permission of the Australian Coeliac Society. By Robert Anderson, MD, Peter Gibson, MD and Finlay Macrae, MD. In 2002, the diagnosis of celiac disease means an end to delicious French pastries and the casual approach to diet that most people in the community enjoy. Today, strict adherence to a gluten free diet is the only effective treatment for celiac disease. A Vaccine for Celiac Disease? The good news is that new research in celiac disease suggests a "vaccine" may be feasible! Such a development has come from a greater understanding of the cause of celiac disease. You might say that we have known the cause of celiac disease for decades—"something" in gluten. But, there is more! We are all exposed to gluten but only some of us get celiac disease. This other factor is the characteristic of the immune system that makes the small intestine a "battleground" when it is exposed to gluten. The exciting advances are twofold. First, we have now identified the "something" in the gluten that makes the immune system angry (that is, the target of the immune response). Secondly, we now understand why only some people's immune system gets angry with gluten—it is all about the genes we carry that control the immune response. How the Advances were Made Almost all individuals with celiac disease have one of two genes involved in the immune response, HLA-DQ2 (90%) or HLA-DQ8 (5%). In the general population only 30% have one of these genes, let's call them A and B. These genes are also very common in early onset diabetes and thyroid disease (both quite commonly associated with celiac disease). A and B have the task of latching on to chunks of proteins (peptides) and carrying them to certain cells in the immune system called T cells. In celiac disease, we know that gluten peptides are indeed taken ("presented") to T cells via A and B. Gluten peptides attached to A and B then activate a proportion of the T cells present in the gut and cause the flattening of the intestinal villi known as villous atrophy— the pathologist's hallmark for diagnosing the disease. Ever since it was shown that gluten causes celiac disease, the challenge faced by researchers was to prove whether there are many, a few, or just one component of gluten that is "toxic"—that is capable of causing this damage. Most researchers thought that a wide range of components of gluten (peptides) were involved in causing celiac disease, and indeed a range of T cells reacting against various gluten peptides were found. This would have meant that the idea of a vaccine to abort this immune process to gluten (a process technically called "tolerance") was impractical. However, these early experiments with T cells were unable to show what really happened when gluten was exposed to the immune system in "real people" with celiac disease. Our work performed in Oxford, and to continue at The Royal Melbourne Hospital, Box Hill Hospital and Walter and Eliza Hall Institute in Melbourne, utilizes T cells from celiac subjects that have recently eaten gluten-containing bread. T cells induced by eating gluten could be measured in blood. To our surprise, these T cells initially targeted only one small component of gluten (a small peptide) in the most toxic fraction of wheat gluten (alpha-gliadin). Whether different peptides in the other components of wheat, rye and barley gluten are targets to which T cells react in patients with celiac disease is currently under investigation. How a Vaccine Might Work In animal diseases, the understanding of how T-cells respond is much further advanced than in humans. In fact, it has been possible to prevent and even treat animal diseases caused by T cells by "vaccinating" with T-cell target peptides. For example, nasal administration of peptide can prevent a mouse disease similar to multiple sclerosis. It "blocks" the subsequent immune response which is the hallmark of the disease. Why can't we do this in celiac disease? Celiac disease is the first human condition for which there is a clear understanding of the T-cell targets—a peptide in gluten. In work that is now planned in Melbourne, the possibility of a "vaccine" for celiac disease will be tested. The first stage of this project will begin in the next six months. But even if successful, it is still likely to be ten years or more before a "treatment" is ready for general use. These studies may provide celiac disease with its first alternative to a gluten free diet. Welcome back French pastries and crusty bread!

Celiac.com 01/23/2023 - Celiac disease is an auto-immune condition in which eating gluten damages the intestinal lining of the gut. Currently, the only proven celiac treatment is a gluten-free diet. However, perfect gluten-free compliance is hard to sustain, and accidental gluten exposure is common. Studies show that even the most diligent patients likely get exposed to small doses of gluten on a regular basis. Because of this, there is substantial interest in developing new drugs and therapies to treat celiac disease, usually in tandem with an existing gluten-free diet. A team of researchers recently set out to review existing and upcoming clinical trial programs for pharmacologic agents for celiac disease. The research team included Michael Klonarakis; Christopher N. Andrews; Maitreyi Raman; Remo Panaccione; and Christopher Ma. They are variously affiliated with theDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; the Division of Gastroenterology & Hepatology, University of Calgary, Calgary, Alberta, Canada; the Alberta Collaboration of Excellence for Nutrition in Digestive Diseases, Calgary, Alberta, Canada; and the Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. Their team conducted a narrative review by searching MEDLINE, Embase, the Cochrane CENTRAL Library and clinicaltrials.gov. They then summarized the pathophysiology of celiac disease and the specific steps that could be favorably influenced by pharmacologic treatment, and then assessed the evidence in favor of current and future drug targets, including trials of peptidases, gluten sequestrants, tight junction regulators, anti-transglutaminase 2 therapies, immune tolerizing agents, advanced biologics and small molecules, and microbiome-targeted strategies. Finally, they highlighted the variables key to conducting successful celiac disease trials, including finding suitable study groups, evaluating results in the context of a gluten challenge, and interpreting celiac-specific clinical and histologic outcomes. After balancing these factors and accurately appraising the evidence, the team described potential celiac disease pharmacotherapies of the future. From their assessment, the team concludes that celiac disease sufferers need pharmacologic options, either to complement a gluten-free diet in the case of gluten exposure, or for treating refractory disease. With numerous drugs currently in development, the team expects approvals for the first generation of celiac drug treatments within the next 5 years. Color me skeptical, but the idea that new and effective treatments for celiac disease are only 5 years away is one we've heard for at least 15+ years now. The failures are legion. However, any major step forward will give people with celiac disease much to look forward to, so here's hoping. Stay tuned for more on this and related stories. Read more in Alimentary Pharmacology & Therapeutics

Celiac.com 01/13/2023 - Celiac disease is an autoimmune disorder in which gluten consumption triggers gut damage. The only effective treatment is a strict gluten-free diet. Can hookworms help celiacs eat gluten? The answer is yes and no, coupled with some trade-offs. Here's the rundown. Earlier studies have indicated that hookworm infection may restore some level of gluten tolerance in celiac patients, however, none of these approximately one dozen studies were placebo controlled. We've done a number of articles on hookworms and celiac disease. We've even done an article on health claims from at least one hookworm-infected celiac patient who claimed he was able to safely eat gluten. Can Hookworms Help Celiacs Eat Gluten? To get a more detailed answer, a research team recently undertook a randomized, placebo-controlled trial of hookworm infection in nearly sixty people with celiac disease. The team included John Croese, MD; Gregory C. Miller, FRCPA; Louise Marquart, PhD; Stacey Llewellyn, BSc; Rohit Gupta, FRACP; Luke Becker, BAppSci; Andrew D. Clouston, PhD; Christine Welch, FRACP; Julia Sidorenko, PhD; Leanne Wallace, BSc; Peter M. Visscher, PhD; Matthew L. Remedios, FRACP; James S. McCarthy, MD; Peter O'Rourke, PhD; Graham Radford-Smith, PhD; Alex Loukas, PhD; Mark Norrie, PhD; John W. Masson, FRACP; Richard B. Gearry, PhD; Tony Rahman, PhD; and Paul R. Giacomin, PhD. They are variously associated with the Department of Gastroenterology and Hepatology at The Prince Charles Hospital in Brisbane, Australia; the Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia; the Envoi Specialist Pathologists, Brisbane, Australia; the QIMR Berghofer Medical Research Institute, Brisbane, Australia; the Department of Gastroenterology, Townsville University Hospital, Townsville, Australia; the Institute for Molecular Bioscience at the University of Queensland, Brisbane, Australia; the Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Australia; the Gastroenterology and Hepatology, Logan Hospital, Brisbane, Australia; and the Department of Medicine, University of Otago, Christchurch and Canterbury District Health Board, Christchurch, New Zealand. Study Ran Nearly Two Years In a study that ran for just under two years, a research team of medical professionals treated celiac patients with with a placebo, or with either third stage larvae of the 20 or 40 Necator americanus hookworm (L3-20 group or L3-40 group). Patients then increased their gluten consumption to 5 grams per day for 12 weeks, 1 gram intermittent twice weekly for 12 weeks, and two grams sustained for six weeks, followed by liberal diet for 1 year. About forty to fifty percent of hookworm patients, and about fifty-five percent of placebo subjects made it to the main outcome point of 42 weeks, and hookworm-treated participants did show a sharp reduction in gluten-related events. Duodenal villous height: crypt depth deteriorated similarly compared with their enrollment values in each group, with an average change of −0.6 for the placebo group; -0.5 for the L3-20 group , −1.1 for the L3-40 group. A retrospective analysis showed that nearly one in four L3-treated participants failed to develop successful hookworm infection. Lower Quality of Life Scores for Hookworm Patients Between forty to fifty percent of participants in each group completed the study, but quality of life symptom scores after the gluten challenge were under forty percent in hookworm-positive participants, compared with over forty-five percent for the hookworm negative group. From their findings, the team concludes that hookworm infection DOES NOT restore gluten tolerance enough to allow sustained moderate consumption of gluten of two grams per day or more. However, hookworm infection did lead to better symptom scores after occasional consumption of lower doses of gluten. The findings undercut the idea that hookworm infection is some kind of magic bullet for gluten consumption for people with celiac disease. Hookworm Infection Not a Magic Bullet for Celiacs At best, the data support the idea that hookworm infection can help reduce symptoms of moderate gluten consumption in people with celiac disease, but that any reduction also likely comes with a lower overall quality of life score. This is the most definitive study we've yet seen on the effects of hookworm infection on the ability of celiac disease patients to tolerate gluten. The results are clear that any modest benefits of hookworm infection comes with some potential reduction in quality of life. Still, the ability of hookworms to help reduce symptoms of moderate gluten consumption in people with celiac disease merits further study. It's possible that hookworms hold some secrets in their biochemistry that might help to offer some extra protection against the inflammation triggered by limited gluten consumption. That is some exciting news. Read more at: Clin Transl Gastroenterol. 2020 Dec; 11(12): e00274.

Celiac.com 01/16/2023 - We get a lot of questions about celiac disease and related conditions. Recently, we've seen a lot of questions from people wondering about the difference between Irritable Bowel Syndrome (IBS), and celiac disease. We've done a number of articles on how the two conditions can sometimes have similar symptoms. How do you know which is which? What's the difference in symptoms, diagnosis, and treatment? Celiac disease is an auto-immune condition in which wheat, rye, or barley triggers gut damage. Irritable bowel syndrome (IBS) is a complex gastrointestinal disorder that can cause a significant decrease in patient quality of life. Doctors and researchers still know very little about the origins or triggers for IBS. IBS is More Common than Celiac Disease While celiac disease affects about one percent of the population, IBS affects 10 to 15 percent of the U.S. population. It is more common in women, but can affect individuals of both genders and all ages. IBS and Celiac Can Have Similar Symptoms The cause of IBS remains poorly understood by medical professionals. Experts believe IBS symptoms may have more than one cause. IBS is often marked by numerous symptoms, including abdominal pain, constipation and diarrhea, or both constipation and diarrhea, as well as bloating, nausea and vomiting. The most common symptom associated with IBS is abdominal pain. Symptoms of celiac disease can include diarrhea, constipation, nausea, vomiting, stomach cramps, gas and bloating, or weight loss. Some people also have anemia, acid reflux or heartburn, itchy skin rashes or blisters, numb or tingly feet or hands, joint pain, headaches, mouth sores, or damage to tooth enamel. However, many IBS symptoms are also common in celiac disease. To make matters more confusing, numerous studies have shown that a high percentage of patients with IBS are also sensitive to gluten. Even though many of these symptoms can mimic celiac disease, most people with IBS typically do not have celiac disease. In addition to celiac disease, a number of other diseases can mimic IBS, including inflammatory bowel disease, bacterial infections, colon cancer, and thyroid disease. These diseases typically show more severe symptoms, including rectal bleeding, weight loss and low blood counts, which are not normally seen in patients with IBS. However, IBS does not lead to an increased risk of cancer. No Easy Way to Diagnose IBS Whereas many conditions, like celiac disease, can be spotted by screening, examinations or testing, IBS is a disease that requires ruling out other contains for a diagnosis. Once other diseases and conditions are ruled out, IBS is often left as the only option standing, and so becomes the the accepted diagnosis. Rule Out Other Diseases to Diagnose IBS In order to diagnose IBS, other diseases, including celiac disease, must first be ruled out. That usually means a celiac disease blood screen, and possibly a colonoscopy or upper endoscopy. It also typically means screens and tests to rule out other conditions with similar symptoms. Easy to Rule Out Celiac Disease While some of the symptoms of IBS and celiac disease can be similar, it's usually fairly easy to test for celiac disease, and to rule it in or out based on screening results. Unlike people with celiac disease, most people with IBS do not suffer from damage to the intestinal villi. Most people with IBS will test negative for a celiac disease blood screen, and show no celiac-associated gut damage. Obviously, patients with celiac disease rarely also have IBS. So, if celiac disease is diagnosed, that's usually the end of the confusion. If celiac disease is ruled out, then the diagnostic journey can continue until other possible conditions and diseases are ruled out as well. Treatment for IBS Unlike celiac disease, where a gluten-free diet usually resolves symptoms and returns normal gut health, treatment of IBS is largely a matter of managing the symptoms. First treatment options should start with diet. If you suspect you have IBS, it's good to keep a food journal. Write down everything you eat and drink, and how you feel afterward. Try to eliminate any foods or drinks that seem to cause symptoms. Gluten-Free Diet Helps Some IBS Patients Many patients with IBS respond to a gluten-free diet. However, a gluten-free diet is typically not recommended for the treatment of IBS. That's because it usually won't resolve the symptoms on its own, and many people with IBS do seem to tolerate gluten with no issues. Low FODMAP Diet Helps Some IBS Patients One recent study shows that IBS patients on a low FODMAP diet show marked reduction in IBS symptom severity, along with reduced levels of fecal calprotein after the gut microbiota return to normal. If your doctor suspects IBS, it's best to consult a dietician or nutritionist before you embark on a gluten-free or a low-FODMAP diet. Typically, foods that may trigger symptoms are slowly reintroduced into the diet after about six weeks. In addition to dietary measures, psychological interventions, such as counseling and exercise, have been shown to improve IBS symptoms. Yogurt Can Help Resolve IBS Symptoms A recent study shows that homemade yogurt resolves IBS symptoms in most patients. Medicine Can Help Control IBS Symptoms Unlike celiac disease, medicines, such as peppermint oil, fiber, minimally absorbed antibiotics, anti-nausea medications, anti-diarrheal medication, laxatives, anti-spasmodics and anti-depressants, can sometimes help improve IBS symptoms. Probiotics are not typically used to treat IBS, but might be an option based on your particular symptoms. Check with your doctor. Exercise and Counseling Can Help IBS Patients Regular gentle exercise, such as walking, yoga and swimming are helpful for IBS. Exercise helps to relieve stress, release anti-oxidants and endorphins, and improve gut health. Some research indicates that alternative therapy, including acupuncture, yoga, hypnosis, meditation, and physical therapy, may help to alleviate IBS symptoms. Counseling, especially cognitive behavioral therapy, can also help IBS patients to keep an eye on their GI symptoms. No cure for IBS Unlike celiac disease, in which gut damage usually reverses, and symptoms usually improve, on a gluten-free diet, IBS cannot be cured. But IBS can be managed to achieve minimal symptoms. Therapy for IBS must be tailored for each patient, usually in consultation with the physician, often by trial and error. There are many great resources available for IBS patients, including helpful websites, support groups, and phone apps to track symptoms and food intake. Though IBS can be painful and confusing, many patients improve once they are diagnosed and begin to work actively to reduce symptoms and manage the condition. Read more at WebMD.com

Celiac.com 12/19/2022 - Major drug firms Takeda, Zedira, and Dr. Falk Pharma GmbH, have announced a collaboration and licensing agreement to develop ZED1227/TAK-227, a Phase 2b investigational drug for the treatment of celiac disease. According to the Takeda press release, TAK-227 is a selective, oral small molecule designed to inhibit tissue transglutaminase (TG2), an enzyme that generates immunogenic gluten peptide fragments upon the breakdown of gluten in the gut. TAK-227 is a potential first-in-class therapy designed to prevent the immune response to gluten in celiac disease. It works by "targeting the dysregulated transglutaminase to prevent mucosal damage in the small intestine by preventing the body’s immune response to gluten, a disease process mediated by activation of gluten-specific T cells," according to Takeda A Phase 2a proof-of-concept study published in the New England Journal of Medicine showed that, in addition to being safe and well tolerated during a six-week gluten challenge, TAK-227 conveyed a protective effect on the duodenal mucosa, and celiac-related symptoms. “Patients with celiac disease urgently need appropriate therapeutic options to manage the significant negative impacts of the disease on health and daily quality of life,” said Roland Greinwald, Ph.D., Managing Director Medicine & Pharmaceutics at Dr. Falk Pharma The collaboration agreement gives Takeda exclusive license to develop and commercialize ZED1227/TAK-227 in the United States and countries outside of Europe, Canada, Australia and China, and adds a third investigational drug to Takeda’s development pipeline for celiac disease treatment. Obviously, any drug that can help to prevent mucosal damage in the gut when people consume gluten will be interesting and potentially helpful to a great many people with celiac disease. We'll need to keep an eye on the details, especially any side-effects, and the degree of protection, etc. to know for sure. Still, the deal is important because it reiterates the companies' commitment to this celiac disease drug, and to continue doing the heavy lifting in developing other drugs to treat celiac disease. Stay tuned for more on this and related stories. Read more in the Takeda Press Release

Celiac.com 04/07/2021 - It is not uncommon for people with celiac disease to have ongoing digestive symptoms and other systemic problems, even on a gluten free diet. Even though celiac disease is becoming better understood each year, much remains to be learned about the effects of the disease on the body and its ongoing symptoms. Not everyone with celiac disease who goes on a gluten-free diet will recover, according to the following study: "After an average of 11 months on a gluten-free diet, 81% of patients with celiac disease and positive tissue transglutaminase IgA (tTG-IgA) at baseline will revert to negative tTG-IgA (SOR: C, disease-oriented evidence from retrospective cohort study). The intestinal mucosa of adult patients with celiac disease will return to normal after following a gluten-free diet for 16 to 24 months in only 8% to 18%. However, in children after 2 years, 74% will have a return to normal mucosa (SOR: C, diseaseoriented evidence from longitudinal studies)." While this article is intended to address celiac-related issues that you may want to explore with your health care provider, it is not intended as medical advice. Please consult a physician for any medical advice related to celiac disease or any issues mentioned in this article. Celiac Disease Follow Up Treatment A number of follow up tests are recommended, both immediately after a celiac disease diagnosis, and on an ongoing basis, including: Blood work for vitamin and mineral deficiencies Micronutrient deficiencies are common in adults with celiac disease, as are vitamin and mineral deficiencies. The most common vitamin and mineral deficiencies in celiac patients include the following vitamins and minerals: B vitamins (especially B12); Vitamin A; Vitamin D; Vitamin E; Vitamin K; Iron; Calcium; Carotene; Copper; Folic acid; Magnesium; Selenium; and Zinc. Thyroid Screening Because celiac disease is linked to autoimmune thyroid disease, thyroid screening is recommended for newly diagnosed celiac disease patients. (Note: Patients on thyroid replacement and other medications may need frequent monitoring for dosage adjustment as their absorption improves.) Bone Density Scan Up to 75% of celiac patients have low bone mineral density. Because of this, bone density scans are recommended for newly diagnosed celiacs. Liver Enzymes Research from Stanford University School of Medicines Celiac Management Clinic is noting continued absorption problems with many individuals who are on a gluten free diet. A 72 hour quantitative fecal fat test and a 25-gram xylose sugar absorption test can help diagnose continued absorption problems. Healing progress on the gluten-free diet may be monitored by re-testing whichever diagnostic blood test was initially highest, at an interval of 6 - 12 months. Children are likely to heal within a few months; adults may take a few years, and some may never totally heal. Note: Calcium and Iron status will improve in most individuals, even without supplements, once the gut heals. Several doctors recommend NOT prescribing drugs such as Fosamax and Evista until after the intestine heals and more calcium is being absorbed from the diet. Celiac Disease and Ongoing Symptoms After a Gluten-Free Diet Most individuals will experience a significant decrease of symptoms within a few weeks or months of starting a gluten free diet. However, some individuals may continue to experience significant digestive problems or may have a relapse of symptoms. Some possible explanations are summarized below: Hidden Gluten Exposure New research shows that most people with celiac disease are regularly exposed to gluten, even when they are trying to be careful. Moreover, for most celiacs, gluten exposure is usually ongoing and silent. This article explores how much gluten exposure do celiacs get on a gluten-free diet. Moreover, celiac patients are really bad at judging gluten-exposure based on symptoms. Look for any possible sources of gluten exposure. Consider binders in medication, cross contamination, misunderstanding of the strictness required of the diet, etc. Repeat blood tests might give an indication of continued gluten exposure; however these may not be sensitive enough to note low level exposure. Many celiacs report positive results after taking AN-PEP enzymes (GliadinX is a brand that we've reviewed) before meals whenever they eat outside their homes. These enzymes have been shown in multiple studies to effectively break down small amounts of gluten in the stomach, before it reaches your intestines. Lactose Intolerance Enzymes needed to digest lactose are manufactured by the intestinal villi, which, in celiacs, are damaged by exposure to gluten. Many people with celiac disease suffer intolerance to casein, a protein found in dairy products. Often, this intolerance subsides as the gut heals. Lactose intolerance is a common misdiagnosis in celiac patients, because the mucosal damage from gluten leaves them unable to digest lactose-containing products. Testing for lactose intolerance can be done with a hydrogen breath test, Lactose H2. Suggested treatment includes using an over-the-counter lactose enzyme when ingesting dairy products. Re-colonizing the small intestine with probiotic bacteria (see probiotics below) is also helpful. How is lactose intolerance related to celiac disease? Helicobacter Pylori A study by Villanacci, et. al, published 8/28/2006 in the American Journal of Gastroenterology noted that 44% of individuals diagnosed with celiac disease tested positive for helicobacter pylori at the time of, or within 1 year of their celiac disease diagnosis. Interestingly, patients with helicobacter pylori colonization have a decreased risk of celiac disease. An Iranian study showed a connection between helicobacter pylori and celiac disease. Small Bowel Bacterial Overgrowth In a report published in the American Journal of Gastroenterology, Vol. 98, No. 4, 2003 of 15 persons with continuing symptoms, 10 showed evidence of overgrowth of bacteria within the small bowel. Testing included Lactulose H2 breath testing. Suggested treatment includes the non-systemic, prescription antibiotic, Rifaximin (800 mg. per day for one week). Note that the antibiotic used is called Rifaximin in England and Xifaxam in the U.S. Digestive function should also be evaluated as the underlying cause of SBBO. For more information, check these related articles: Breath Tests for the Non-invasive Diagnosis of Small Intestinal Bacterial Overgrowth: A Systematic Review With Meta-analysis, and Rosacea and Small Intestinal Bacterial Overgrowth (SIBO). Yeast Overgrowth Some individuals report continuing symptoms due to overgrowth of yeast. Testing includes blood antibody testing for Candida. Suggested treatment includes ½ tsp Nystatin powder (mix with water), twice a day and 200 mg Ketoconizole once per day for 2-3 months. Monthly liver function testing during treatment is recommended. Nystatin powder may be ordered, by prescription, through pharmacies which offer custom compounding of medications. Digestive function should also be evaluated as the underlying cause of yeast overgrowth. Dietary changes may also be considered. Other Food Sensitivities Additional IgG food sensitivities may be seen. An IgG sensitivity is different from the IgE allergies most allergy doctors check for. Common food sensitivities include dairy casein, corn, soy and eggs. Treatment includes avoiding the food, and food rotation. There are some reports of a reduction of food sensitivities when digestive function improves. To begin an elimination diet, it makes sense to start with the top most common food allergens, as identified by regulatory agencies like the FDA (U.S. Food and Drug Administration) and health organizations like the CDC (Centers for Disease Control and Prevention), and eliminate them one at a time for 2-3 weeks, then add the item back and record any symptoms or issues you might have. It might make sense to start this process in this order: Milk Eggs Peanuts Tree nuts (such as almonds, cashews, walnuts) Soy Fish Shellfish (such as shrimp, crab, lobster) Sesame seeds Mustard Dr. Fasano has created a diet for those with celiac disease which seems to help most celiacs improve quickly. Lately, there's also been focus on FODMAPS (See below). A low FODMAP diet has been shown to help reduce symptoms of IBS. This older article also has some interesting ideas. Cross-Reactivities for Celiac Patients A recent study indicates that Silicon Dioxide (Food additive E551) May Trigger Intestinal Damage and Inflammation in People with Celiac Disease or Gluten Sensitivity. Cross-reactivity between anti-gliadin antibodies and certain spice proteins indicates that patients with celiac disease or wheat allergies may also have an intolerance to many spices, even if they are gluten-free. Some spices can also be a source of cross-contamination, as wheat flour may be used as an anti-caking agent. This article explores this topic in more detail: Beyond Gluten: Exploring Lesser-Known Triggers and Cross-Reactivities for Celiac Patients Digestive Function Multiple problems with digestive function may be found. A complete evaluation should be done. One source for a comprehensive stool analysis may be obtained, by mail and by prescription. Intestinal Motility Increased intestinal motility may contribute to continuing diarrhea. Try reducing motility by using a fiber supplement like Benefiber or Citracel. Particularly in individuals who have had their gall bladder removed, consider Cholestid, a prescription drug used for lowering cholesterol, which may also slow motility. It acts by binding to irritating bile salts. Decreased Stomach Acid Low stomach acid (hypochlohydria) may interfere with the effectiveness of digestive enzymes, and promote yeast or bacterial overgrowth. A good source of information is the book "Why Stomach Acid is Good for You" by Wright & Lenard. For testing, using the Heidleberg Capsule or Gastrocap tests. Some celiacs with low stomach acid find benefits from taking supplemental Betaine HCl, bitters, digestive enzymes and probiotics, available at a health food store. Related articles include: Reduced Fecal Acidity Mirrors Rise in Celiac Rates. Beneficial Bacteria Probiotics are very helpful for regaining the balance of the intestinal flora. Use products that have multiple types of bacteria. Those found in the refrigerated section of health food stores will have the highest level of bacteria. Kefir, raw kimchee and raw sauerkraut, also found in the refrigerated section, have high levels of active cultures. Related articles include: Celiac Disease Onset Changes Gut Microbiota in Children; What Can Gut Microbiomes Teach Us About Gastrointestinal Distress in Children?; and Gut Microbiota Reflects Disease Severity in COVID-19 Patients. Digestive Enzymes Pancreatic enzymes assist with more complete digestion, discouraging unhealthy bacterial growth. Many people with celiac disease prefer vegetable based enzymes. which may be purchased online, or at health food stores. Animal derived enzymes are available by prescription. Experiment to see what works best. To prevent heartburn, start by sprinkling ½ of a capsule on food, and increase as needed and tolerated. Be sure to make sure your enzymes are gluten-free. Watch out for Maltase, which can often be made from barley. Related articles include: Are Gluten-Busting Enzymes the Best Hope for Future Celiac Treatment and Maintenance?; Could Enzymes from Oral Bacteria Treat Celiac Disease?; Researchers Review Potential of Gluten Degrading Enzymes for Treatment of Celiac Disease; and Imagine a Gluten-Busting Enzyme that Worked Like LactAid. Carbohydrate Intolerance Some individuals do not digest carbohydrates and sugars well. The undigested carbohydrates encourage the growth of harmful yeasts and bacteria. More information on a diet low in carbohydrates may be found in the book "Breaking the Vicious Cycle" by Gottschall, who recommends eliminating all complex carbohydrates to kill off "bad" bacteria. Parasites and other Bacterial Problems Check for parasites and other bacterial problems, including Giardia lamblia and Ascaris lumbricoides. Just because an individual has celiac disease, doesn't mean they cant have the bugs that a normal person with diarrhea may have! Other Autoimmune Diseases A number of autoimmune conditions are associated with celiac disease. At least one in three people diagnosed with adult celiac disease will also have another autoimmune disease. Many report a significant improvement in their other autoimmune disease after beginning a gluten free diet. However, some individuals with celiac disease may develop other autoimmune diseases even after beginning a gluten free diet. Watch for Type 1 diabetes, liver, thyroid, pancreas and adrenal diseases, peripheral and central nervous system damage, connective tissue and other rheumatoid inflammations. Related articles include: Celiac Disease is Linked to Autoimmune Thyroid Disease; and The Ten Risk Factors Most Associated with Celiac Disease. FODMAPS FODMAPs is an acronym, short for “fermentable, oligosaccharides, disaccharides, monosaccharides and polyols.” FODMAPs is a single name for a bunch of different molecules, common in many in foods, that are poorly absorbed by some people. People who can’t tolerate FODMAPs can suffer celiac-like gastrointestinal symptoms. A low FODMAP diet has been shown to help reduce symptoms of IBS, and could be helpful to some people with celiac disease. FODMAPs have also been shown to play a role in non-celiac gluten sensitivity (NCGS). Now, a new app can help people zero in on FODMAPs in food. Related articles include: Can Low FODMAP Diet App Help Some Celiac and IBS Patients?; What's the Deal with FODMAPs and Gluten-sensitivity in IBS?; and FODMAPs, Food Intolerance and You. Oxalate Sensitivity Oxalate sensitivity can lead to inflammation in certain individuals due to the body's inability to properly metabolize oxalates, which are naturally occurring compounds found in many foods. When these oxalates accumulate in the body, they can form crystals that deposit in tissues, leading to inflammation and pain. This condition, often linked to disorders like kidney stones, can exacerbate inflammatory responses in the gut, joints, and other tissues, particularly in those with compromised gut health or certain genetic predispositions. The inflammatory response triggered by oxalate crystals can contribute to symptoms such as joint pain, digestive issues, and even chronic fatigue, making it crucial for sensitive individuals to manage their oxalate intake. Lectin Sensitivity Lectin sensitivity can cause inflammation in some individuals due to the body's adverse reaction to lectins, which are proteins found in various plant foods such as beans, legumes, and grains. Lectins can bind to carbohydrate molecules on the surfaces of cells, including those in the gut lining, potentially disrupting the gut barrier and leading to increased intestinal permeability, also known as "leaky gut." This disruption can trigger an immune response, resulting in inflammation and contributing to symptoms such as digestive issues, joint pain, and fatigue. In sensitive individuals, reducing or avoiding high-lectin foods may help alleviate these inflammatory responses and improve overall health Article originally published 03/25/2007, updated 04/07/2021.

Celiac.com 12/16/2022 - Recently, an interesting discussion thread popped onto our celiac disease and gluten-free forum. A member of the forum, going by the handle @dixonpete, claims his celiac disease went into remission after treatment with hookworms. Moreover, he claims that he is essentially cured, and able to eat gluten with no side effects, and has had at least one recent negative follow up tTG antibody test to back this up. History of Hookworm Infection to Treat Celiac Disease We've done more than a few articles on the potential to use hookworms to treat celiac disease. We've done a number of articles on hookworms as the potential future of celiac disease treatment, including: Are Intestinal Worms the Future of Autoimmune Disease Treatment? Could Hookworm Infections Help Cure Celiac Disease? Celiac Patients Tolerate Wheat Spaghetti After Hookworm Treatment Have Celiac Disease? Try a Little Hookworm with that Pasta! Previously, we'd only reported data from various studies, some of which looked promising. Until recently we had never heard directly from anyone claiming to have gone through hookworm treatment firsthand. Because he is the first person we've heard from who claims direct experience with hookworm treatment for celiac disease, the information furnished by @dixonpete to the thread might be of interest to anyone who might be interested in the possibility of receiving hookworm treatment. Hookworms seem to work, at least partly, by blocking the inflammatory response in the gut of the host. One of the benefits of this treatment is that the hookworms may also block the gut's immune response to gluten in people with celiac disease. Could Hookworm Treatment Allow Celiacs to Eat Gluten Again? At this time, there's no data to confirm that hookworm treatment "cures" celiac disease in the classic sense of the word. In theory, if the hookworms were eliminated, then the celiac disease could return. And the hookworms don't reproduce, so you need just the right amount in the gut, but not too much. The current hypothesis is that the hookworms simply block the immune inflammatory response when people with celiac disease eat gluten. But even that remains unclear, and not well-supported by data. Clearly more studies need to be done to verify whether hookworms present a viable alternative for people with celiac disease. A single example of this possibly working in real life isn't enough data to support the claim that the treatment should work for all celiacs. In fact, @dixonpete admits himself that he was suffering from both celiac disease and other conditions that drove his decision. Still, it's a compelling story. For more information, read the full discussion thread and the related articles. If hookworms prove to be effective treatment for celiac disease, would you be willing to consider a hookworm infection to treat your celiac disease? Let us know in the comments below.

Celiac.com 11/21/2022 - Following a gluten-free diet for life can be difficult, Most celiacs on a gluten-free diet get exposed to gluten on a regular basis, especially if they eat in restaurants. Currently, a gluten-free diet is the only effective treatment for celiac disease. Because of this, there is substantial interest in drug therapies that can help to protect celiacs on a gluten-free diet, and, ideally, free them from a strict gluten-free diet. There are a number of drugs still in the pipeline that promise the former, at least. So what's the status of the multiple new therapies that are under investigation? To answer this question, a team of researchers recently set out to review existing and upcoming clinical trial programs for pharmacologic agents for celiac disease. The team conducted a narrative review using searches of MEDLINE, Embase, the Cochrane CENTRAL Library and clinicaltrials.gov. In their review, the team summarizes the pathophysiology of celiac disease, and the specific steps that might help to speed pharmacologic treatment. They also assess the evidence in support of current and future drug targets, including trials of peptidases, gluten sequestrants, tight junction regulators, anti-transglutaminase 2 therapies, immune tolerizing agents, advanced biologics and small molecules, and microbiome-targeted strategies. The team also spotlights the special challenges of conducting celiac disease trials, including identifying appropriate study populations, assessing results in the context of a gluten challenge, and interpreting celiac disease-specific clinical and histologic outcomes. Understanding these factors is crucial for accurately appraising the evidence. Finally, they outline what the future of celiac disease therapy may hold with the introduction of viable drug treatments. There is a definite need for drug options for treating celiac disease, either for accidental or intentional gluten exposures, as part a gluten-free diet, or for refractory disease. The big takeaway, is that, according to the team's reading of the data, multiple promising celiac disease drug therapies are in development, and these trials are likely to lead to approvals for the first generation of pharmacologic agents for celiac disease within the next 5 years. Color us skeptical, but that seems a pretty bullish view, especially given the crowded graveyard of once seemingly promising celiac drug therapies, especially the very recent demise of the highly touted Larazotide. Basically, we'll believe in successful drug treatments for celiac disease when we see a successful product make it to celiacs. Meanwhile, stay tuned for more on this and related stories. Read more in Aliment Pharmacol Ther. 2022;55(10):1277-1296 The research team included Michael Klonarakis, Christopher N. Andrews, Maitreyi Raman, Remo Panaccione and Christopher Ma. They are variously affiliated with theDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; the Division of Gastroenterology & Hepatology, University of Calgary, Calgary, Alberta, Canada; the Alberta's Collaboration of Excellence for Nutrition in Digestive Diseases, Calgary, Alberta, Canada; and the Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

Celiac.com 09/21/2022 - The dream of creating a safe, effective drug that can help people with celiac disease to tolerate small amounts, or perhaps even large amounts, of gluten. Until its recent failure, 9 Meters' larazotide was the only celiac drug in Phase 3 clinical trials. The recent discontinuation of larazotide, based on disappointing interim results, highlights the unmet need for effective alternatives to a gluten-free diet for treating celiac disease. Larazotide's failure also opens the doors for current and future Phase 1 and Phase 2 celiac therapies to be first-to-market. It also highlights the lack of a good lineup of potential new drugs. The reality is that, with the collapse of several once promising candidates, the bench for viable alternative celiac disease treatments is shallow, at best. Current Celiac Disease Pipeline Therapies Include: Latiglutenase (ImmunogenX) PRV-015 (Provention Bio, Inc. with Amgen) TAK-101 (Takeda Pharmaceuticals) ZED-1227 (ZEDIRA GmbH) KAN-101 (Anokion SA) In an effort to assess the current and future alternatives for treating celiac disease without a gluten-free diet, data marketing company Spherix recently interviewed one-hundred US gastroenterologists, and conducted eight qualitative interviews to compile a report on the issue. Spherix has issued a recent report on the form gastroenterologists engaged in a thorough review of these pipeline product descriptions (based on publicly available clinical information for each product). The report assesses celiac diagnostic and treatment trends emerging, as well as physician reactions to potential therapies in the pipeline. The 2022 report reveals a greater sense of urgency from gastroenterologists versus the 2021 report. Indeed, the number of respondents in the 2022 survey who say that their celiac patient load has increased in the past year, is up by 60% over 2021. Read more at PRNewswire.com

Celiac.com 10/11/2022 - Enzymes that can break down gluten in the stomach before it gets to the gut are a potentially important therapy tool for people with celiac disease. In people with celiac disease, the digestion of gluten creates peptides, including the strongly immunogenic proline-rich 33-mer from wheat α-gliadin, that trigger auto-immune reactions in the gut, along with associated villi damage, when untreated. Having a therapy that could reduce the abundance of the 33-mer in the small intestine could be very helpful to many people with celiac disease. Neprosin is the latest candidate. A team of researchers recently set out to test a glutamate-class prolyl-endopeptidase for celiac disease therapy. The research team included Laura del Amo-Maestro, Soraia R. Mendes, Arturo Rodríguez-Banqueri, Laura Garzon-Flores, Marina Girbal, María José Rodríguez-Lagunas, Tibisay Guevara, Àngels Franch, Francisco J. Pérez-Cano, Ulrich Eckhard & F. Xavier Gomis-Rüth. They are variously affiliated with the Proteolysis Laboratory at the Department of Structural Biology, Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park in Barcelona, Catalonia, Spain; the Section of Physiology; Department of Biochemistry and Physiology; Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Catalonia, Spain; and the Research Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona in Barcelona, Catalonia, Spain. Neprosin from the pitcher plant is a reported prolyl endopeptidase. As part of their effort, the team produced recombinant neprosin, along with several mutants, and revealed that full-length neprosin is a zymogen, which is self-activated at gastric pH by the release of an all-β pro-domain via a pH-switch mechanism featuring a lysine plug. The team describes the catalytic domain, in which the action occurs, as an atypical 7+8-stranded β-sandwich, with an extensive active-site cleft holding an unprecedented pair of catalytic glutamates. The researchers found that neprosin quickly and effectively breaks down both gliadin and the 33-mer in vitro under gastric conditions. The action can be reversibly inactivated above pH 5. Moreover, administering gliadin and the neprosin zymogen together at the ratio 500:1 reduces the abundance of the 33-mer in the small intestine of mice by up to 90%. A 90% reduction in the 33-mer means that a substantial reduction in the ability of the protein to trigger an immune response in people with celiac disease. Neprosin therefore represents a family of eukaryotic glutamate endopeptidases that meets the parameters for an effective therapeutic glutenase. The development of effective therapeutic glutenase products remains a top priority for many researchers, with the potential to benefit huge numbers of people with celiac disease, many of whom are subject to accidental gluten ingestion on a regular basis. Read more in Nature Communications volume 13, Article number: 4446 (2022)