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Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.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
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.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.
Scott Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 03/19/2009 - Numerate Inc., a biotechnology company leveraging a novel drug engineering process to design lead-stage drug compounds, announced today it has received a Phase 1 grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH). The Small Business Technology Transfer (STTR) award, entitled “Drug Engineering of Transglutaminase 2 Inhibitors,” will be used to support a research collaboration between Numerate and the laboratory of Chaitan Khosla, Ph.D., the Wells H. Rauser and Harold M. Petiprin Professor of Chemical Engineering and Chemistry at Stanford University. “This NIH Phase 1 STTR award validates the attractiveness of Numerate’s drug engineering process for the design of new small molecule drugs,” stated John Griffin, Ph.D., Numerate’s chief scientific officer and principal investigator of the project. “In addition, it recognizes the potential of transglutaminase 2 inhibitors for the treatment of Celiac Sprue. Professor Khosla is a leader in Celiac disease research, and we are pleased to have the support of the NIH in our collaboration with him and his laboratory.” Professor Khosla, who will serve as co-investigator for the STTR research project, added, “Transglutaminase 2 is central to the pathophysiology of Celiac Sprue, and offers a compelling target for a disease for which no pharmacotherapy currently exists. I look forward to having Numerate apply its breakthrough technology to this important problem.” Celiac Sprue, also known as celiac disease, is an autoimmune disorder of the small intestine involving intolerance to gluten proteins found in wheat and other grains. About Numerate Numerate is a privately held biotechnology company that has developed and extensively validated a drug engineering process that rapidly and cost-effectively delivers small molecule drug candidates optimized for efficacy, safety, and patentability. Numerate’s drug engineering process combines advances in computer science, statistics, and molecular modeling to address, in parallel, the factors that determine the success and failure of a drug. Numerate applies this proprietary process to design and develop small molecule therapeutics in collaboration with a variety of partners in the pharmaceutical and biotechnology fields. For more information, please visit www.numerate.com.