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Celiac.com 06/29/2024 - Celiac disease is an autoimmune disorder where ingesting gluten leads to damage in the small intestine for those genetically predisposed. The standard treatment for celiac disease is a strict gluten-free diet, which, while effective, can be challenging to maintain and does not always completely prevent symptoms or intestinal damage. This has led researchers to explore new therapeutic approaches aimed at improving the lives of those with celiac disease. These novel therapies fall into five main categories: modulating the immune response to gluten, eliminating gluten before it reaches the intestine, inducing gluten tolerance, modulating intestinal permeability, and restoring a healthy gut microbiota. Modulating the Immune Response One promising area of research involves therapies that block the presentation of gluten peptides by HLA-DQ2 and HLA-DQ8, which are gene variants strongly associated with celiac disease. Three therapies in this category show significant promise: TPM502: This therapy uses three gluten-specific antigenic peptides that interact with T-cells associated with the HLA-DQ2.5 gene. A Phase 2a clinical trial is evaluating the safety and effects of TPM502 in adults with celiac disease. This trial is randomized, placebo-controlled, and involves multiple centers. Patients receive two infusions of TPM502 or a placebo, with the dose escalating through four cohorts to determine the optimal dosage. The study aims to monitor safety, tolerability, and pharmacodynamics. KAN-101: Designed to induce gluten tolerance, KAN-101 targets specific receptors in the liver. The study for KAN-101 is a three-part trial that includes an open-label, multiple ascending dose phase, followed by two double-blind, placebo-controlled phases. Part A of the study assesses the safety and tolerability of KAN-101, while Parts B and C focus on the response to gluten challenges and biomarker responses. This therapy has received Fast Track designation by the US Food and Drug Administration, highlighting its potential to address unmet needs in celiac disease treatment. DONQ52: This is a multi-specific antibody targeting HLA-DQ2. The ongoing clinical trial for DONQ52 involves two parts: a single ascending dose phase and a multiple ascending dose phase, both designed to evaluate the safety and tolerability of the drug in patients with well-controlled celiac disease. This trial aims to understand how the drug behaves in the body and its impact on biomarkers related to celiac disease. Eliminating Gluten Before It Reaches the Intestine Another approach is to prevent gluten from reaching the small intestine, thereby avoiding the immune response altogether. This strategy involves enzymes that break down gluten peptides in the stomach before they can cause harm. While specific therapies in this category are not detailed in the study, the concept is based on reducing the exposure of the small intestine to gluten, thereby preventing the autoimmune reaction. Inducing Gluten Tolerance Inducing gluten tolerance aims to retrain the immune system to tolerate gluten without triggering an autoimmune response. KAN-101 is a notable example in this category, as it seeks to create immune tolerance by targeting receptors in the liver. This approach could potentially allow people with celiac disease to consume gluten without adverse effects. Modulating Intestinal Permeability Celiac disease often increases the permeability of the intestinal lining, allowing gluten peptides to enter the bloodstream and trigger an immune response. Therapies that modulate intestinal permeability aim to strengthen the intestinal barrier. By doing so, these treatments can prevent gluten peptides from passing through the intestinal wall and reduce the overall immune response. Restoring Gut Microbiota Balance The gut microbiota plays a crucial role in overall health and immune function. In people with celiac disease, the balance of gut bacteria is often disrupted. Therapies in this category aim to restore a healthy balance of gut microbiota, which could help reduce symptoms and improve gut health. This approach includes the use of probiotics and other microbiota-modulating treatments. Conclusion The development of novel therapies for celiac disease offers hope for improved management and quality of life for those affected. These therapies, which range from immune modulation to restoring gut microbiota, are still in various stages of clinical trials but show promise in addressing the limitations of a gluten-free diet. For individuals with celiac disease, these advances could mean more effective treatment options and a better ability to manage their condition without the strict dietary restrictions currently required. The ongoing research and clinical trials are a crucial step toward finding more comprehensive solutions for celiac disease, potentially transforming the standard of care in the near future. Read more at: medscape.com sciencedirect.com nature.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 03/27/2017 - A number of researchers are looking to provide alternative or adjunct treatments to the gluten-free diet in celiac disease. Meanwhile, a number of companies are currently developing a wide variety of such options, ranging from various kinds of enzyme therapies, to treatments that eliminate celiac disease reactions, even to vaccines to inoculate celiac sufferers against their condition, perhaps allowing for full recovery and a return to non-gluten-free eating habits, as desired. At least, that's one dream. More likely will be the development of enzymes or other treatments that offer celiacs varying degrees of protection from gluten ingestion. Most likely, such treatments would be designed to augment an existing gluten-free diet, and to provide protection against moderate gluten-contamination when eating out. One particular enzyme that shows strong potential in breaking down toxic peptides in A-gliadin, the main culprit in celiac reactions, is caricain. A recent paper discusses the scientific principles behind the use of caricain for enzyme therapy. The paper is based on a recent study, in which a team of researchers set out to review the structures of the toxic peptides in A-gliadin for key sequences of amino acids or motifs related to toxicity, especially with respect to digestive difficulties, or immunogenicity. The research team included Hugh J. Cornell and Teodor Stelmasiak. They are affiliated with the RMIT University, School of Applied Sciences, Melbourne, Australia, and with Glutagen Pty Ltd, Maribyrnong, Victoria, Australia. For their study, they first evaluated structures of synthetic A-gliadin peptides shown to be toxic in the fetal chick assay, both before and after digestion with duodenal mucosa from patients in long remission. They also measured synthetic peptides corresponding to the undigested residues, and compared the key amino acid sequences, to see if they might be related to direct toxicity and immunogenicity of the peptides. They found that the smallest toxic peptides from celiac mucosal digestion were octa-peptides, which they found in greater amounts than similar products from normal digestion. One of those peptides corresponded to residues 12-19 of A-gliadin and contained the key motifs PSQQ and QQQP of De Ritis et al., while the other corresponded to residues 72-79, and contained the key motif PYPQ (extending to PYPQPQ). These key motifs have been noted by other workers, especially those investigating immunological activity over the past two decades. They are present in undigested residues from celiac mucosal digestion These motifs, along with the greater prevalence of these residues, as compared with residues from normal digestion, supports the basic notions underpinning enzyme therapy for celiac disease. This study also supports the basic scientific merits of research and development of the enzyme caricain to break down gliadin peptides with two different types of toxicity, and thus to potentially benefit people with celiac disease. Source: International Journal of Celiac Disease. Vol. 4, No. 4, 2016, pp 113-120. doi: 10.12691/ijcd-4-4-2 Previous study: NCBI

Celiac.com 03/31/2014 - Celiac disease is an autoimmune disorder that occurs in genetically susceptible individuals who carry the genetic markers HLA DQ2 or DQ8. About one in three people carry these genetic markers, while researchers estimate that the global prevalence of celiac disease is somewhere between one- and two-percent. A gluten-free diet remains the only treatment for celiac disease, but researchers are looking into new therapies aimed at gluten modification. A team of researchers have reviewed a number of promising new celiac disease therapies aimed at gluten modification. The researchers include S. Stoven, J.A. Murray, and E. Marietta, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine at the Mayo Clinic in Rochester, Minnesota. Their review in Clinical Gastroenterology & Hepatology discusses gluten-based therapies including wheat alternatives and wheat selection, enzymatic alteration of wheat, oral enzyme supplements, and polymeric binders as exciting new therapies for treatment of celiac disease. Unfortunately, the full study is only available to subscribers, but anyone with the inclination to subscribe can read it online. Source: Clin Gastroenterol Hepatol. 2012 Aug;10(8):859-62. doi: 10.1016/j.cgh.2012.06.005.