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Celiac.com 12/03/2024 - Understanding celiac disease has advanced significantly over recent years. From novel treatments to groundbreaking insights into the immune system’s response to gluten, these research breakthroughs are paving the way for new therapies and more accurate diagnoses. Here are five recent advances you’ll want to know about if you or someone you know is affected by celiac disease. 1. Exploring the Gut-Brain Connection in Celiac Disease Scientists have long recognized the importance of the gut-brain connection, and it’s now a major focus in celiac research. Celiac disease doesn’t just affect the digestive system; it’s also linked to neurological symptoms like anxiety, depression, and brain fog. Recent studies show that inflammatory markers in the bloodstream may cross the blood-brain barrier in people with celiac disease, leading to brain inflammation. This discovery has opened the door to new ways of treating neurological symptoms in those with celiac disease. Future therapies may target inflammation in the brain, improving mental health and cognitive function for those with the condition. 2. Targeted Immune Therapies to Reduce Gluten Sensitivity While a vaccine like Nexvax2 hasn’t been successful in trials, and the immune-targeting therapy larazotide acetate has also failed in trials, another promising development in celiac research is ZED1227, an experimental drug specifically designed to inhibit the body’s inflammatory response to gluten. ZED1227 works by blocking transglutaminase 2 (TG2), an enzyme that plays a critical role in the immune reaction to gluten. By targeting TG2, ZED1227 aims to prevent the immune system from attacking the gut lining when gluten is ingested, which could significantly reduce symptoms and intestinal damage for people with celiac disease. Early clinical trials have shown that ZED1227 is both safe and effective at reducing inflammation in response to gluten exposure, even in small amounts. While it’s not a cure and doesn’t replace a gluten-free diet, ZED1227 could offer a valuable safety net for individuals at risk of accidental gluten ingestion. If further trials continue to show positive results, ZED1227 could become the first medication designed to protect against gluten-induced damage, representing a major advancement in celiac disease management. 3. Enzyme Therapy as a Gluten Defense One promising area of celiac research involves enzymes designed to break down gluten before it reaches the small intestine. Scientists are investigating various enzyme therapies that could help people with celiac disease digest gluten more effectively. These enzymes, when taken as a supplement, aim to neutralize gluten before it causes damage. Although these enzymes won’t replace a gluten-free diet, they could reduce the severity of reactions after accidental gluten exposure. Enzyme therapy is currently in clinical trials, with researchers optimistic about its potential to provide a new layer of protection for those with celiac disease. 4. New Diagnostic Tests for Earlier and More Accurate Detection Diagnosing celiac disease traditionally requires a combination of blood tests and a biopsy, but researchers are exploring non-invasive alternatives. For instance, one study focused on developing a simple breath test to detect celiac-specific markers in the gut. This new method could allow for faster and less invasive screening, helping to identify celiac disease earlier in life. Early diagnosis is crucial to avoid long-term complications, such as osteoporosis and other autoimmune disorders. As these tests become more refined, they promise to simplify the diagnosis process and make it more accessible. 5. Advances in Personalized Nutrition and Microbiome Research The unique composition of each person’s gut microbiome may affect the severity of their celiac symptoms, and recent research has uncovered connections between the gut microbiome and gluten sensitivity. Scientists are studying how different bacterial strains in the gut influence immune responses to gluten. This research could lead to personalized dietary recommendations and probiotic treatments tailored to each individual’s microbiome. By adjusting gut bacteria to support digestive health, this approach may help manage symptoms more effectively and even enhance the body’s ability to tolerate small amounts of gluten. 6. CRISPR-Modified Wheat: Gene Editing for Gluten-Free Grains In a groundbreaking approach to celiac disease, scientists are exploring the use of CRISPR gene-editing technology to develop gluten-free wheat. By targeting the specific genes responsible for gluten proteins in wheat, researchers aim to “turn off” or modify the genes that trigger the immune response in people with celiac disease. Unlike traditional gluten-free options, this modified wheat would maintain the texture and nutritional profile of regular wheat, potentially providing a much-needed alternative for baking and cooking. While still in development, CRISPR-modified wheat holds great promise for those with celiac disease, offering the possibility of enjoying wheat-based products without risking an immune reaction. Early research has shown success in reducing specific gluten proteins, and with further refinement, CRISPR-modified wheat could become a viable, naturally gluten-free option. This innovation could revolutionize food choices and significantly improve quality of life for individuals with celiac disease. Looking Ahead: Hope for the Celiac Community With these advancements, the future looks brighter for those living with celiac disease. While a strict gluten-free diet remains the primary treatment, these breakthroughs represent meaningful progress in understanding and managing the disease. From vaccines and enzyme therapies to early diagnostics and microbiome research, each of these areas holds promise for improved quality of life. As research continues, the celiac community can look forward to more personalized and effective treatments, allowing for a more balanced and less restrictive lifestyle. Until then, staying informed and connected with medical updates can empower those affected by celiac disease to make educated choices about their health. Watch the video version of this article:

Celiac.com 09/09/2024 - Celiac disease is an autoimmune disorder affecting about one percent of the global population. Those with celiac disease must adhere to a strict gluten-free diet, as there is currently no other treatment option available. A recent study by researchers at Stanford University and the Stanford Synchrotron Radiation Lightsource at the U.S. Department of Energy's SLAC National Accelerator Laboratory has provided new insights into the key enzyme transglutaminase 2 (TG2), which plays a significant role in the disease's pathology. The Function of Transglutaminase 2 Transglutaminase 2 is a multifunctional enzyme involved in various physiological and pathological conditions, including celiac disease. The enzyme requires calcium to perform its primary chemical reactions, transamidation and deamidation. These reactions are crucial because they enable TG2 to modify gluten peptides in a way that triggers the immune response seen in celiac disease. Specifically, TG2 deamidates certain glutamine residues in gluten peptides, creating a strong immune response that leads to the body attacking its own intestinal tissues. Structural Analysis of TG2 One of the significant achievements of this study was obtaining a high-resolution X-ray crystallographic structure of TG2 bound to calcium. This structure revealed the conformations of TG2 when interacting with calcium, providing detailed insights into its catalytic cycle. The researchers identified two key calcium-binding sites, S1 and S3, which play distinct roles in the enzyme's function. The S1 site regulates the formation of an inhibitory disulfide bond, while the S3 site is essential for the formation of γ-glutamyl thioester, an intermediate state crucial for TG2's activity. Mechanistic Insights into TG2 Activity The study uncovered several important mechanistic details about TG2. Two residues, H305 and E363, were found to be critical for resolving the thioester intermediate into an isopeptide bond, a key step in the transamidation process. However, these residues do not play a role in thioester hydrolysis, which is involved in deamidation. Additionally, residues N333 and K176 help stabilize TG2 substrates and inhibitors by forming hydrogen bonds with nonreactive backbone atoms. These findings provide a more comprehensive understanding of how TG2 functions at a molecular level and how it transitions between different states during its catalytic cycle. Implications for Drug Development The insights gained from this study are not just of academic interest; they have practical implications for drug development. By revealing the detailed structure and mechanisms of TG2, the researchers have provided a valuable framework for designing better therapeutic inhibitors of the enzyme. Currently, drugs targeting TG2 are being developed for celiac disease and other related conditions, such as idiopathic pulmonary fibrosis. This study's findings can inform the design of these drugs, potentially leading to more effective treatments. Conclusion This research represents a significant step forward in understanding the molecular mechanisms underlying celiac disease. By elucidating the structure and function of TG2, the study provides crucial insights that could lead to the development of new treatments for celiac disease. For those affected by this condition, these advancements offer hope for alternatives to the strict gluten-free diet that currently remains the only effective treatment. The findings underscore the importance of structural biology in uncovering the intricacies of disease mechanisms and paving the way for innovative therapeutic approaches. Read more at: pnas.org and phys.org

Celiac.com 03/25/2023 - Researchers reported last month that they have discovered the cause of celiac disease: A small fragment of the gluten protein fails to break down and triggers the immune systems into action. In addition to discovering the key fragment that makes gluten so poisonous to celiacs, Dr. Chaitan Khosla, researcher and founder of the Celiac Sprue Research Foundation (CSRF), reports that he has also found a bacterial enzyme that breaks down the toxic peptide and appears to make gluten digestible and safe. The enzyme could well become the key to an oral medication for celiac disease. The CSRF is a science-driven public charity that seeks to improve the quality of life of celiac patients by promoting research and development, and by enhancing awareness of the disease among scientists, healthcare professionals, consumer product manufacturers and the general public. Its primary goal is to translate emerging knowledge about celiac disease into a comprehensive plan for developing a therapeutic alternative to a gluten-free diet. Once the Foundation’s initial drug development strategy has been launched, it will use available resources to promote basic research that might lead to fundamentally new insights into the disease, and to improve technologies for detecting new patients of this seriously under-diagnosed disease. It is anticipated that each of the therapeutic possibilities being researched by the CSRF will require 1-3 years of pre-clinical research before a suitable Investigational New Drug (IND) candidate can be identified for further clinical studies. Once an IND application has been successfully filed with the U.S. FDA or its European equivalent, extensive human clinical studies must be performed to thoroughly assess both the safety and efficacy of the drug candidate. These clinical trials can be expected to last 5-8 years before a prescription drug emerges in the marketplace. Until such studies are successfully completed, no candidate therapeutic agent can be considered suitable for use by celiac sprue patients. The CSRF has ambitious and achievable goals if it can gain the immediate support of the celiac community. The CSRF is actively raising funds to help support the above research and development efforts.

Celiac.com 04/29/2020 - People with celiac disease cannot eat gluten from products made with wheat, barley or rye. The two main culprits proteins in gluten are glutenin and gliadin, with the latter thought to cause most of the inflammation and adverse health health effects in people with celiac disease. Glutenases are enzymes needed to break down glutens in foods to make these foods easier for people to digest. Imagine an enzyme that could be added to traditional wheat or gluten-containing products to make them gluten-free. The technology would work very much the way adding lactase to regular milk breaks down the lactose proteins and makes the milk safe for people with milk intolerance. It's a very cool idea. One major hurdle involves the fact that glutenase enzymes that break down gluten proteins can't take the high temperatures used to manufacture or process food. Researchers Seek Enzymes to Break Down Gluten in Food Production A team of researchers at Clemson University may have solved that problem, or all least made strong progress. Sachin Rustgi, an assistant professor of molecular breeding in Clemson’s Advanced Plant Technology Program, is working with numerous other to create glutenases capable of withstand high cooking temperatures. In addition to Rustgi, others involved in the study are: Claudia Osorio, Nuan Wen, Diter von Wettstein and Shannon Mitchell of Washington State University, and Jaime H. Mejías of Institute of Agricultural Research (INIA), Chile. Early results from their study show that it's possible to create glutenase enzymes that can handle the high temperatures required to manufacture or process foods. However promising, the results are merely preliminary, and further study will be needed before the full results will be known. Such an enzyme might allow manufacturers to add glutenases to food labeled ‘gluten-free’” Rustgi said. “This will allow people with celiac disease to tolerate foods that are contaminated with gluten/wheat." Alternatively, such an enzyme could allow researchers to engineer wheat grains that incorporates such glutenases into its structure. "After necessary testing, this may provide an alternative treatment for celiac disease,” Rustgi said. Imagine traditional bread that was gluten-free and made safe to eat through the addition of enzymes. Few things would be more promising to people with celiac disease. Stay tuned for more on the efforts to develop enzymes that can break down gluten, and potentially help people with celiac disease to avoid damage from accidental gluten-ingestion. Read more at Newsstand.clemson.edu

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)

Celiac.com 12/01/2020 - Lipase is an enzyme that breaks down fats into glycerol and fatty acids, which can help reduce the possibility of obesity and weight gain. The global market for Lipase enzyme is projected to grow substantially over the next decade, largely as a result of the increased production of food and dairy products. Increasing consumption of fatty and carbohydrate rich food items has helped drive an increase in health-related diseases, like obesity and celiac disease, but also in adverse symptoms such as bloating, abdominal discomfort and indigestion. According to the World Health Organization, nearly 40% of adults aged 18 years and over are overweight, while nearly 15% are obese. Rising numbers of people with obesity, celiac disease, high cholesterol, and high triglycerides, along with a desire to reduce rates of health diseases have helped increase global demand for Lipase enzyme. In addition to the healthcare industry, where emerging biosensors technology is expected to drive lucrative growth opportunities, Lipase enzyme also enjoys rising demand from the food and dairy industry as a flavor enhancer. A recent report by Futuremarketinsights.com, Lipase enzyme Market Latest Technology and Market Trends & Forecast – 2028, offers in-depth insights on crucial aspects of the global Lipase enzyme market and offers insight on important market segments, growth and competition patterns, along with other factors fueling market growth. Get a sample of the report, Lipase enzyme Market Latest Technology and Market Trends & Forecast – 2028. Read more at kerryvillebreakingnews.com

Celiac.com 06/11/2019 - A potentially major breakthrough in celiac disease treatment owes at least part of its success to a simple drive-in hamburger from Seattle's beloved and legendary Dick's Drive-In. If you have celiac disease, and haven't heard of PvP Biologics, you likely will. PvP originated in 2011 as an award winning student biology project at the University of Washington Institute for Protein Design, a lab that has created several successful startups. PvP's enzyme-driven product, KumaMax, is designed to break down gliadin, the part of gluten that triggers an autoimmune reaction in people with celiac disease and gluten sensitivity. Like most similar enzyme therapies, KumaMax is not designed to be a cure for celiac disease, but to help prevent adverse reactions from accidental gluten contamination. KumaMax is designed to break down gluten in the stomach, and to help prevent a gluten reaction. Celiac.com covered part of the PvP story in 2017 in our article "Takeda Taps PvP Biologics to Develop Celiac Disease Therapy." That story covered PvP's deal with Japanese drug giant Takeda, which gave the startup $35 million to complete a phase 1 clinical trial, at which point Takeda has the option to purchase the startup. Apparently, when it was time for PvP Biologics to test KumaMax, the research team needed to make sure their enzyme would work in the stomach, and work only against gluten proteins, not against meat or dairy proteins. The team wanted a meal that would allow them to test the gluten-neutralizing properties of their drug in conditions that mimicked the human stomach. For that meal, the team turned to Dick's Drive-In, purveyors of fine burgers. “We got a hamburger and a vanilla milkshake from the Dick’s Drive-In in Wallingford,” said Ingrid Pultz, co-founder and chief scientific officer of PvP. “If we were going to get a hamburger, it might as well be from Dick’s. It’s a Seattle institution.” Team members labeled the food as lab equipment. They then blended and acidified the mixture, to mimic the stomach environment, and added the KumaMax enzyme. The enzyme worked well enough to become PvP's lead molecule, and to earn the support of Takeda. So there you have it. KumaMax, the breakthrough gluten dissolving enzyme that may offer celiacs some protection against accidental gluten ingestion has its roots in a simple hamburger and milkshake from Seattle institution, Dick's Drive-In. Read more at Geekwire.com

Celiac.com 05/13/2020 - With the collapse of the Nexvax 2 'vaccine" for celiac disease, which was really more like allergy therapy, but which has been abandoned after poor results in clinical trials, the hope for an outright cure, or "silver bullet" treatment for celiac disease seems a far-off possibility. That means that people with celiac disease are unlikely to gain immunity to gluten, and start freely eating gluten any time soon. Unlike a vaccine, which would theoretically make it possible for people with celiac disease to eat gluten, enzymes do not change the underlying celiac disease at all. People with celiac disease still have celiac disease, and need to follow a gluten-free diet to maintain optimal health. However, gluten-busting enzymes seem to hold the most promise for helping people with celiac disease to avoid accidental gluten ingestion, and to promote better overall health. New revelations from real world studies that show that even the most diligent celiacs are often exposed to gluten offer strong arguments in favor of using gluten targeting enzymes. Arguments Against Enzymes Arguments against enzymes include the idea that such enzymes might lead celiacs to deliberately consume gluten. There are good reasons why this viewpoint doesn't stand up too well to scrutiny. Anyone who would risk their health to deliberately consume gluten likely doesn't need an enzyme as an excuse to do so. Any extra protection against gluten contamination would seem to be a good idea for most celiacs, even those who willingly cheat on their diets, which some surveys put at over 20% of celiacs, especially in light of data that shows that many gluten-free people with celiac disease are accidentally, and unknowingly exposed to low levels of gluten that can trigger symptoms and cause gut damage. Other studies show that adverse gluten reactions are common in people with celiac disease on a gluten-free diet. Eating away from home, especially at restaurants and other homes, carries the greatest risk for gluten exposure. Arguments in Favor of Enzymes Arguments in favor of enzymes often include the idea that enzymes are unlikely to harm patients, and could provide an extra measure of protection against minor accidental gluten ingestion by people with celiac disease. Especially in sensitive people, the argument goes, enzymes could offer some protection. That argument has been borne out by the studies showing that most gluten-free celiacs are regularly exposed to gluten in their diets. There are currently numerous enzymes on the market that claim to break down gluten to one degree or another. Most of these enzymes target gluten in general, but one, AN-PEP, has been shown in several studies to break down gluten in the stomach before it gets to the intestine. This could be a crucial development in celiac disease treatment and management. Enzymes that Claim to Break Down Gluten AN-PEP AN-PEP, derived from the from aspergillus niger fungus, AN-PEP is one of the most promising enzymes. It has been clinically proven to break down gluten in the gut. There are several brands of aspergillum niger, including Gliadin-X. Kiwifruit Recent research shows that the kiwifruit produces enzymes that are great at breaking down gluten proteins, and could be effective supplements. Papaya The product, called GluteGuard, is based on a papaya fruit enzyme called caricain. This papaya enzyme is shown to be helpful for celiac patients. A 2015 study showed adding caricain to bread dough reduced gluten toxicity to gluten by 90% for celiac patients. Carnivorous Plant Enzymes Remember all those cool plants, like Venus Flytraps and Pitcher Plants, that eat bugs? Enzymes from carnivorous plants are excellent at breaking down the proteins that make up the plant's diet. Studies show that these enzymes are also great at breaking down gluten proteins. Latiglutinase Celiac patients appear to show symptomatic and QOL benefit from using latiglutenase with meals. Enzymes from Oral Bacteria A recent study of oral bacteria concludes that gluten-degrading Rothia and food-grade Bacillus subtilisins are the "preferred therapy of choice for celiac disease," and that their exceptional enzymatic activity, along with their connection to natural human microbial colonizers, make them "worthy of further exploration for clinical applications in celiac disease and potentially other gluten-intolerance disorders." Few Oral Enzymes Break Down Gluten in the Stomach Oral enzymes that break down gluten in the gut offer the best hope for most celiac patients in the near term. One enzyme in particular, AN-PEP, which is derived from aspergillum niger, has been clinically shown to break down gluten in the stomach, before it reaches the intestine. Breaking down gluten proteins before they reach the intestine, and provoke an immune reaction in celiacs, is key to any oral enzyme. As such, AN-PEP seems to hold tremendous promise. Gluten-Busting Enzymes Could Change Food Manufacturing Researchers at Clemson University are working to produce active enzymes that can be added to products to make them gluten-free, in much the same way that lactase enzymes are used to make lactose-free milk. Obviously many hurdles need to be cleared, and much testing and refinement must happen, but, in theory, such products would be safe for people with celiac disease. A growing body of evidence shows that enzymes may have a beneficial role to play in helping people with celiac disease to minimize potential damage from accidental gluten ingestion, which happens more frequently than previously thought. The key will be finding ways to deploy these enzymes that are proven to provide protection for people with celiac disease looking to follow a gluten-free diet, including oral enzymes that break down gluten in the gut, and possibly even in products that contain wheat, rye, or barley. Stay tuned for more developments on the role of enzymes in celiac disease treatment and management.

Celiac.com 05/06/2020 - Naturally occurring enzymes, such as papain enzymes from papaya, or aspergillus niger, have shown promise in breaking down dietary gluten in the stomach before it gets to the gut. The latest addition to that list of potentially helpful enzymes is the kiwifruit, that brown, hairy egg-shaped fruit with a sweet, tart, green flesh and edible black seeds. Long known for being rich in vitamins, and generally good for digestion, the kiwifruit is getting a second look for its potential to break down gluten. Scientists at New Zealand's Riddet Institute scientists are testing the ability of natural fruit enzymes to break down gluten proteins into smaller pieces that will not trigger the classic inflammatory response seen in people with celiac disease. Kiwifruit naturally contains a protein-digesting enzyme called actinidin, which could provide some protection for celiacs who accidentally consume small amounts of gluten-containing foods. So far, lab tests show kiwi to be the little fruit that could. In lab tests, actinidin has been shown to break gluten into smaller, easier to manage pieces. In theory, that might mean reduced inflammation in celiac patients who consume gluten. The research team is currently testing actinidin on models of the human digestive tract. More research will show whether actinidin can break down gluten in the human gut. Recently, the Riddet research team completed a study that showed that modern food production methods do not trigger or worsen gluten intolerance. If the kiwifruit enzyme proves effective in breaking down gluten, the next step will be to assess the best way to use the enzyme to help people with celiac disease. Because kiwifruit is already rich in dietary fibre, vitamin C and other nutrients, kiwifruit enzyme therapy could offer have an advantage over similar products on the market. Stay tuned for more stories on the future of enzyme therapy in celiac disease treatment. Read more at Stuff.co.nz.

Celiac.com 12/24/2019 - Celiac disease is a common autoimmune disease triggered by dietary gluten that can lead to severe gastrointestinal symptoms. The only current treatment is a lifelong gluten‐free diet, but many patients continue to have chronic symptoms. Could enzyme therapy help these people? A team of researchers recently set out to assess the effectiveness of the oral enzyme latiglutenase, for improving multiple gluten‐induced symptoms and patient quality of life (QOL) due to accidental gluten consumption by celiac patients on a gluten‐free diet. The researcher team included Jack A. Syage, Peter H.R. Green, Chaitan Khosla, Daniel C. Adelman, Jennifer A. Sealey‐Voyksner, and Joseph A. Murray. They are variously affiliated with ImmunogenX, Newport Beach, CA, USA; Celiac Disease Center, Columbia University, New York, NY, USA; Stanford University, Stanford, CA, USA; Aimmune Therapeutics, Brisbane, CA, USA; and the Division of Gastroenterology and Hepatology, Mayo Clinic For the study, 398 symptomatic celiac patients received doses of either latiglutenase or placebo for 90 days, and responded to a daily symptom diary, along with multiple QOL questionnaires at weeks 0, 6 and 12 of the treatment periods as secondary endpoints. The results were organized according to patient antibody levels. The reults showed a statistically significant and dose‐dependent improvement in seropositive, but not seronegative, celiac patients. In subjects receiving 900 mg latiglutenase, improvements (P‐values) in the severity of these symptoms for week 12 were 58% (0.038), 44% (0.023), 21% (0.164) and 104% (0.049) respectively, compared with those receiving a placebo. Overall, the greater the symptoms, the greater the relief seen in symptomatic patients. Similar results were seen in QOL reports. Although the results do not show a clear benefit of latiglutenase in seropositive celiac patients across the board, they do seem to show an improvement in the severity and frequency of symptoms, including abdominal pain, bloating, tiredness and constipation, and in QOL for such patients taking latiglutenase with meals. Targeted enzymes, such as latiglutenase could play a role in improving symptoms and quality of life in celiac patients with ongoing sensitivity and symptoms, even while following a gluten-free diet. Going forward, look for more study, and more investigation into the value of targeted enzymes in treating celiac disease. Read more at the International Journal of Gastroenterology and Hepatology Funding disclosures for the study: Clinical trial NCT01917630 was sponsored by Alvine Pharmaceuticals; all data from this trial is presently owned by ImmunogenX. The data analysis reported here was supported in part by a grant from the National Institutes of Health (R01 DK063158 to CK).

Celiac.com 01/02/2019 - Way back in 2011, a team genetic engineering researchers at the University of Washington began to develop a new treatment for celiac disease. The team’s early research suggested that an oral enzyme that could break down the gluten proteins would be an ideal therapy for celiac disease. Taken before meals by a person with celiac disease, such an enzyme would ideally neutralize all trace of gluten before they could trigger an immune response. Their search to develop such a treatment would take them nearly a decade of effort. To fuel their goals, the team made use of pioneering computer software, called the Rosetta Molecular Modeling Suite, that helps design new proteins, including enzymes. They began by selecting a protein-digesting enzyme that was already known to work well in acidic conditions. However, the selected enzyme lacked the gluten-killing ability the team sought. Using a video game-like interface to Rosetta called Fold-it, the team created versions of the enzyme that would target gluten proteins. The team then chose about 100 of their most promising enzyme designs. They then physically created each of those designer enzymes in the lab and tested their ability to break down gluten. By combining the best performing enzymes, the team was able to create a prototype gluten-degrading enzyme, which they named KumaMax, as it is derived from the starter enzyme, kumamolisin. After years of additional tweaking of the prototype enzyme at the University of Washington’s Institute for Protein Design, the team was able to begin Phase I clinical trials on KumaMax. If clinical trials go well, the team is looking to follow with testing on human celiac patients. The results could give rise to a new commercially available enzymatic treatment for celiac disease. Read more at: ASCH.ORG

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 02/08/2018 - Have you ever considered being tested for a genetic defect called MTHFR? If you have a family history of heart disease or stroke, migraines, trouble getting pregnant or have a child with Autism you might want to consider reading on to learn more. These are just a few of the list of conditions linked to MTHFR mutation. Surprisingly, 60% of our population has this mutation and most do not even know what MTHFR is. I recently came up positive myself for MTHFR A1298C. We will talk more about the two common markers in a bit. This changes everything when it comes to choices and is important to have the knowledge when choosing foods and supplementation. It's also important to monitor your folate levels. More to come. Interestingly, Untreated celiac disease may be associated with hyperhomocysteinemia caused by a combination of vitamin deficiencies and variants in the MTHFR gene. If you are not healing with a gluten free diet this might be a test to consider. [1] So, what is MTHFR? The MTHFR gene (methylenetetrahydrofolate reductase) is an enzyme that plays an important role in processing amino acids, the building blocks of proteins. Now you know why it's an acronym! Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the vitamin folate (also called vitamin B9). This enzyme converts a molecule called 5,10-methylenetetrahydrofolate to a molecule called 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds. [2] Although, there are over fifty known MTHFR variants, two are commonly tested C677T and A1298. Some of the key things methylation process is responsible for are: Cellular Repair – DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome (genetic material of an organism). Detoxification and Neurotransmitter Production – The interconversion of amino acids. Healthy Immune System Function – Formation and maturation of red blood cells, white blood cells and platelet production. What's the Difference Between the Two Most Common Types? The 677T Variant is associated with heart disease and stroke whereas the 1298C is associated with a variety of chronic illness. Either one however can cause general health problems. Homozygous vs Heterozygous An organism can be homozygous dominant, if it carries two copies of the same dominant allele (allele - one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome.), or homozygous recessive, if it carries two copies of the same recessive allele. Heterozygous means that an organism has two different alleles of a gene. If you are homozygous (2 abnormal copies) your enzyme efficiency drops to 10% - 20% of normal which can be problematic. A more serious combination is 677T/1298C which has both genetic anomalies. If you are having symptoms and can't quite put your finger on it I would suggest getting tested for the MTHFR. That will help your practitioner determine what supplementation best suits your needs. Diet will also be a factor as with MTHFR the body cannot process synthetic folate which is in fortified foods such as cereal, nutritional yeast (can get unfortified), breads, rice, pastas, flour, etc., This explains why I always got a headache after I ate fortified nutritional yeast. I switched to unfortified and I don't have the headaches. As mentioned above, there are many chronic conditions linked to MTHFR. Here are a few: Alzheimer's Autism Autoimmune Disorders Breast cancer Chronic Fatigue Down's Syndrome Fibromyalgia Heart Disease IBS (irritable bowel syndrome) Infertility in both men and women Mental disorders such as bipolar and schizophrenia Migraines Multiple Sclerosis (MS) Sensitivity to chemicals Stroke The Great Detoxifier Glutathione is the body's main antioxidant and detoxifier. What happens with MTHFR mutation is it can make you susceptible to disease by lowering your body's ability to make glutathione. Most people with MTHFR have low glutathione levels. With low glutathione levels, you are more sensitive to toxins and chemicals including heavy metals. The good news is you can supplement glutathione in the correct methyl form and change up your diet. More to come on this. With oxidative stress, we are more likely to have premature aging as well. Another reason to be aware of MTHFR and maintain a healthy high folate diet along with supporting supplementation. Testing If you have any of the symptoms above or have a family history with MTHFR mutations I highly recommend testing for both C677T and A1298. Testing can be done through a practitioner. You can go to 23andme and order the test or work with your health practitioner. It's inexpensive and well worth it. Also, testing your levels of glutathione and folate would be beneficial so your practitioner knows where your levels are before recommending supplementation. Supplementation for MTHFR If you are taking a B vitamin, make sure it's methyl-B12, methyl-folate. Taking synthetic forms (folic acid) can be more harmful than good because the body cannot do the conversion. It's essential to make sure that your method delivers the antioxidant efficiently to your cells. One of the B vitamins I recommend from Pure Genomics is their B Complex available on our marketplace. Glutathione is also important but hard to absorb so a liposome form is recommended or get one with a precursor called NAC (N-acetyl-cysteine). Glutathione is important for detoxification as mentioned. Here are a few to consider – Liposomal Glutathione by Pure Encapsulations as a liposome form With any supplement, you can have adverse effects so make sure you work with a knowledgeable practitioner. Diet and Lifestyle Folic Acid vs. Folate While folic acid and folate may be marketed interchangeably, as mentioned earlier, their metabolic effects can be quite different, especially for those with the MTHFR mutation. Folate is the bioavailable, natural form of vitamin B9 found in a variety of plant and animal foods. Folic acid, on the other hand while readily utilized by the body is synthetic. Folate is found in supplements and fortified foods such as cereals and might I add nutritional yeast. The body is more adept at using folate and regulates healthy levels by discarding excess folate in urine. With MTHFR folic acid can be problematic so make sure you purge the folic acid rich foods and supplements. For those who love the flavor of nutritional yeast and use it in vegan recipes there are a few companies who make unfortified versions you can get off amazon. Daily lifestyle activities such as dry brushing (lymphatic circulation) Epsom salt baths, exercise, sauna's (infrared sauna is amazing) and of course a healthy diet rich in natural forms of folate such as: Beans and lentils Leafy green vegetables including raw spinach Asparagus Romaine Lettuce Broccoli Avocado Bright-colored fruits, such as papaya and orange Here are just a few examples of some folate rich foods. As you can see spinach packs a powerful punch of folate as well as papaya and lentils coming in the highest. [2] Source Spinach Asparagus Papaya Orange Lentils Pinto Beans Sunflower Seeds Serving Size 1 Cup 1 Cup 1 papaya 1 orange 1 Cup 1 Cup ¼ Cup Folate 263 mcg 262 mcg 115 mcg 40 mcg 358 mcg 294 mcg 82 mcg DV % 65% 64% 29% 10% 90% 74% 21% Did you know your liver needs glutathione to produce bile in addition to the detoxification process? Look at addressing health issues such as leaky gut, IBS and Inflammation as these can affect absorption and neurotransmitter levels as well as hormones with MTHFR A1298C mutations. MTHFR mutations are tied to higher mental disorders such as anxiety, depression, bipolar and schizophrenia as well as chronic fatigue and fibromyalgia. It's important to find ways to manage the stressors in addition to healing the gut as symptoms can be heightened with MTHFR. Protect the heart with an anti-inflammatory diet rich in omegas, fiber and plants. Omega 3 and COQ10 supplementation is helpful. A good multi is beneficial as long as you get one with B12 (methyl cobalamin) and Folate (methyl tetrahydrofolate) forms. Drug Interactions to consider You should not use any supplements without first talking to your health care provider. For example, folate should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. Folate is necessary if taking medications for birth control, cholesterol or seizures for example as they may lower folic acid levels in the body. Dosage and timing is important to know. Here are some medications to keep in mind: Antacids, H2 blockers, proton pump inhibitors Bile acid sequestrants Carbamazepine Nonsteroidal anti-inflammatory drugs (NSAIDs) Sulfasalazine Triamterene When taken for long periods of time, these medications, as well as other anti-inflammatory and anti-seizure medicines, can increase the body's need for folic acid. Also consider drugs used for cancer, rheumatoid arthritis and psoriasis as those also reduce the folic acid in the body. Supplementing folic acid can help reduce symptoms of these disorders however with cancer, folic acid may interfere with methotrexates effects on treatment. Talk with your practitioner if you are taking any medications. [3] Knowing your DNA make up is important as is knowing your numbers (blood pressure, cholesterol, etc.) so you can keep a handle on your health and do your best to control stress. Getting tested for the MTHFR mutation is worth knowing whether it comes up or not. It can make all the difference in aging and detoxing and give you a peace of mind. Sources: https://draxe.com/mthfr-mutation/ http://doccarnahan.blogspot.com/2013/05/mthfr-gene-mutation-whats-big-deal.html https://www.jillcarnahan.com/2014/02/23/health-tips-for-anyone-with-a-mthfr-gene-mutation/

Will a new treatment enable people with celiac disease to ditch a gluten-free diet? About one in a hundred people in the United States is affected by celiac disease. If you're one of them, you know how hard it can be to maintain a strict gluten-free diet. Everyone's got their horror stories about trying to simply eat a meal, only to have a tiny amount of gluten wreck havoc on their digestive system. There are currently no therapeutics on the market to treat celiac disease, says Sydney Gordon, a scientist at Ab Initio Biotherapeutics. Sure, there are other over-the-counter enzyme treatments, Gordon adds, but most are slow to act, or don't break down enough gluten to prevent a reaction. "There are no other enzymes on the market for celiac disease," said Justin Siegel, the co-founder of PvP Biologics and an assistant professor of chemistry, biochemistry and molecular medicine at UC Davis. "There is nothing that is approved by the FDA for celiac disease. Nothing has made it through clinical trials. There are pills on the market that cause degradation of gluten, but there is no clinical evidence that they are effective." "We wanted to design an enzyme […] a protein that would act as a therapeutic for celiac disease. We came up with a design using a protein modeling tool called FoldIt," said Ingrid Pultz, a co-founder of PvP Biologics. PvP Biologics enzyme therapy works by targeting the exact triggering molecule, the immunogenic epitope, before it gets to the intestine and causes an immune reaction. To do this, PvP Biologics uses kumamolisin, a naturally occurring enzyme that, unlike some other enzymes, can survive the acidity of the stomach. By modifying the amino acid sequence in the original kumamolisin enzyme, researchers were able to specifically target the epitope causing the reaction. If the therapy proves successful, many celiac patients won't have to worry about minute amounts of cross-contamination when eating outside. Those are pretty strong claims. Many people with celiac disease might likely say that it sounds too good to be true. Still, the company is moving in a direction that few others have gone. No word on if or when we might expect to see a finished treatment come to market. For all the company's claims, there is much to work out, and a long, winding road to get FDA approval. Stay tuned to see if the evidence from trials and from potential consumer use supports those claims. Read more at TheAggie.org. Editor's note: We've received a correction on this story from PvP Biologics, makers of KumaMax, which states that their product is designed for accidental gluten ingestion, and not as a replacement for a gluten-free diet in people with celiac disease. Their enzyme could lessen the effects of accidental consumption of small amounts of gluten.

Celiac.com 07/25/2017 - Enzymes are playing an increasing part in both the treatment of celiac disease, and in the manufacture of gluten-free baked goods. DSM recently showcased their new rice-based baker's enzyme, Bakezyme, at the annual meeting of Institute of Food Technologists (IFT) in Las Vegas. The product took DSM two years to develop and perfect, and promises to improve the softness and moistness of gluten-free bread. Bakezyme is so good, says DSM, and leaves gluten-free bread so soft and so moist that it can compete with wheat-based breads in texture. Designed to meet an array of manufacturer needs, Bakezyme is available in five different enzyme classes–amylase, protease, xylanase, glucose oxidase and amyloglucosidase. The version with amylase, an anti-staling enzyme, for example, will retain the softness for at least nine days. Fokke Van den Berg, DSM global business manager for baking says that Bakezyme grew out of DSM's efforts to tackle the two biggest consumer complaints about gluten-free bread, the hardness, and the dryness. While most baker's enzymes are derived from wheat, Bakezyme is made of fermentation-derived microorganisms added to rice flour, making it suitable for people with celiac disease and gluten intolerance. Because the enzymes are deactivated during baking, Bakezyme is regarded as a processing aid and thus is not required to be listed as an ingredient. DSM tested Bakezyme on two types of dough, oat and a mixture of potato and rice, with each requiring a slightly different formulation for similar results. Beyond the slight costs of ensuring that Bakezyme is gluten-free, its overall price is on par other enzyme ingredients, partly because such a small amount is needed. One kilo of Bakezyme is enough to produce 10,000 kilos of bread. The company expects most demand to come from the US and UK as well as other European countries, but the gluten-free trend is also spreading to Brazil, Turkey and Morocco, said Van den Berg. Read more at FoodNavigator.com.

Celiac.com 09/25/2017 - There are currently several efforts underway to develop successful commercial enzyme treatments for celiac disease. Efforts include looking at the digestive enzymes in plants, such as the papaya and star fruits, including such predatory plants, such as the pitcher plant. One focus has been on developing enzymes that can break down gluten before it can trigger an immune reaction. This could prove helpful to many people with celiac disease. One such enzyme under development is Latiglutenase, formerly known as ALV003. Latiglutenase is a new name for an enzyme therapy designed to be taken with meals. The idea is that a person with celiac disease would take an enzyme tablet with a meal. If the meal had mild gluten contamination, the enzyme’s two recombinant proteins would break gluten into fragments that are not toxic to the immune system, thereby preventing exposure, and symptoms. But the stomach is a notoriously difficult environment to work in, so what seems like a simple idea quite a challenge from a science and biology perspective. Seeking to explore the ability of Latiglutinase to improve symptoms, a team of researchers recently set out to test latiglutenase on celiac patients who are seropositive despite following a gluten-free diet. The research team included Jack A. Syage, Joseph A. Murray, Peter H. R. Green and Chaitan Khosla. They are variously affiliated with the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester USA, the Celiac Disease Center at Columbia University, New York, USA, the Departments of Chemical Engineering and Chemistry, Stanford University, USA, and with ImmunogenX, Newport Beach, USA. "Though the ALV003-1221 trial was inconclusive regarding histologic improvement from latiglutenase, the evidence for symptom benefit, which is more quickly achieved, is quite convincing and clinically relevant," Joseph Murray, MD, of the Mayo Clinic in Rochester, Minn., said in a press release. In these trials, patients with celiac disease who were seropositive despite following a gluten-free diet saw major improvement in symptoms when taking latiglutenase with meals, according to a post hoc analysis of the CeliAction study. The team was really hoping to see histological improvement, but they feel satisfied that this trial shows, says Dr. Murray, that a "therapy to help patients struggling with symptoms due to celiac disease is now within reach." Stay tuned for more on efforts to develop effective enzyme treatments for celiac disease. Read more: Dig Dis Sci. 2017 Doi:10.1007/s10620-017-4687-7.

Celiac.com 10/23/2015 - Just as I finished writing about the failure of current commercial enzymes to effectively degrade gluten, an interesting study on another enzyme suggests that there may be help on the horizon, at least for people without celiac disease. According to the latest press release, in lab conditions, aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides. But so what? If AN-PEP is to be effective in people with celiac disease or gluten-sensitivity, which would seem to be the whole point of an anti-gluten enzyme, it must effectively digest gluten in "non-healthy" subjects. A team of researchers recently set out to assess AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. The research team included B.N. Salden, V. Monserrat, F.J. Troost, M.J. Bruins, L. Edens, R. Bartholomé, G.R. Haenen, B. Winkens, F. Koning, A.A. Masclee. They are variously affiliated with the Division of Gastroenterology-Hepatology in the Department of Internal Medicine at NUTRIM, Maastricht University Medical Center, Maastricht, the Department of Immunohematology and Blood Transfusion at Leiden University Medical Centre in Leiden, the DSM Biotechnology Centre, Delft, the Department of Pharmacology and Toxicology, CARIM, at Maastricht University in Maastricht, and with the Department of Methodology and Statistics, CAPHRI, Maastricht University Medical Center in Maastricht, all in The Netherlands. The team conducted a randomized, double-blind, placebo-controlled, cross-over study in which 12 healthy volunteers attended to four test days. Each volunteer received a liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo administered into the stomach. Using a triple-lumen catheter the team was able to sample gastric and duodenal aspirates, as polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. The team used gastric and duodenal samples to calculate 240-min area under the curve (AUC0-240 min ) of α-gliadin concentrations. The team calculated absolute α-gliadin AUC0-240 min using duodenal PEG-3350 concentrations. The teams data showed that AN-PEP lowered α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 μg × min/mL; P = 0.001). These results confirm that AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers, while increasing caloric density prolonged gastric residence time of the meal. According to the authors, these results suggest that AN-PEP shows promise as an anti-gluten digestive enzyme for people with celiac disease, but further study is clearly needed. Still, the fact that AN-PEP can effectively break down gluten in the stomach of healthy volunteers is a good start, but it means little if AN-PEP can’t do the same in people with celiac disease, which remains to be seen. Stay tuned for more developments. Source: Aliment Pharmacol Ther. 2015 Aug;42(3):273-85. doi: 10.1111/apt.13266. Epub 2015 Jun 4.

Celiac.com 10/02/2015 - Many people with celiac disease or gluten-intolerance take digestive enzymes, hoping for some protection against accidental gluten-contamination. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. However, not all gluten proteins are the same. The gluten proteins that are particularly active in triggering an adverse immune reaction in celiac disease are known as immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. So, how effective are currently available digestive enzyme supplements ineffective in breaking down these specific gliadins that triggers immune reactions in people with celiac disease? A team of researchers recently set out to determine the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP). The research team included G.Janssen, C. Christis, Y. Kooy-Winkelaar, L. Edens, D. Smith, P. van Veelen, and F. Koning. They are variously affiliated with the Department of Immunohematology and Blood Transfusion at Leiden University Medical Centre in Leiden, The Netherlands, DSM Food Specialties, Delft, The Netherlands, and DSM Food Specialties in South Bend, Indiana, USA. For their study, the team subjected each of the five commercially available digestive enzyme supplements along with purified digestive enzymes to 1) enzyme assays and 2) mass spectrometric identification. Gluten epitope degradation was monitored by 1) R5 ELISA, 2) mass spectrometric analysis of the degradation products and 3) T cell proliferation assays. Their findings show that, due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. Basically, none of the currently available digestive enzyme supplements are effective in degrading immunogenic gluten epitopes. This means that these enzymes are not likely to be helpful to people with celiac disease. Share your thoughts in our comments section below. Source: PLoS One. 2015 Jun 1;10(6):e0128065. doi: 10.1371/journal.pone.0128065. eCollection 2015.