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    Discovery of Key Genetic Risk Factor for Celiac Disease Offers Hope of Advances in Diagnosis and Treatment - Results Promise Better Diagnostics and Treatment for Celiac Disease


    Jefferson Adams

    Celiac.com 06/26/2007 - The results of a study recently published in the online science journal Nature Genetics have revealed a previously unknown genetic risk factor for celiac disease. An international team of researchers set out to study the genetic causes of intestinal inflammatory disorders.


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    When the study began, it was well known that individuals with celiac disease have specific tissue types that identify wheat proteins. Why healthy individuals with the same tissue type failed to develop celiac symptoms or celiac disease remained unknown, and was a key question the team set out to answer. The team was led David van Heel, Professor of Gastrointestinal Genetics at Queen Mary, University of London. The Human Genome Project and the Hap Map Project played key support roles in the study.

    The results show that a protective DNA sequence in a specific gene segment, generally found in healthy individuals are missing in people with celiac disease. The research team evaluated genome data of 778 individuals with celiac disease and 1,422 controls non-celiacs within the British, Irish and Dutch populations.

    Key DNA Sequence Missing in Celiacs

    Researchers discovered that, compared to people with celiac disease, healthy people more commonly have a DNA sequence in the interleukin-2 and interleukin-21 gene region that protects against celiac disease. Interleukin-2 and interleukin-21 are cytokine proteins that are secreted by white blood cells, and which control inflammation. In people with celiac disease, the protective DNA sequence most likely leads to lesser amounts of these cytokines being produced, which weakens the defense against intestinal inflammation.

    Breakthrough in Better Understanding Risk Factors for Development of Celiac Disease

    About 1 in 133 people develop the disease, but, so far, predicting those at risk to develop the disease has been haphazard at best. Present methods of genetic testing can only narrow down the search to about 30% of the general population. These results give doctors a means to discover what further genetic risk factors leave people vulnerable to developing celiac disease.

    Queen Mary, University of London Press Release - Public release date: 10-Jun-2007

    health writer who lives in San Francisco and is a frequent author of articles for Celiac.com.
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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Scott Adams
    - Genetic Digestive Disorder Affects an Estimated One in 250 Americans -
    Celiac.com 02/26/2003 - WOODLAND HILLS, Calif., Feb. 19, 2003/PRNewswire -- Results from a new study may lead to the first medical treatment for celiac disease, a hereditary digestive disease that can damage the small intestine and interfere with the absorption of nutrients from food. Celiac disease sufferers cannot tolerate gluten, a protein that is found in wheat, barley and rye. Celiac disease affects an estimated one in 250 Americans, mostly those of European descent, and there is no known medical treatment or cure.
    Zengen, Inc. researchers discovered that a synthetic form of alpha-Melanocyte-Stimulating Hormone (alpha-MSH) has an anti-inflammatory effect in celiac mucosa, the inside lining of the intestinal tract that absorbs food into the body. A naturally occurring molecule, alpha-MSH modulates inflammatory and immune responses. Data confirming the presence of alpha-MSH in celiac mucosa suggests the presence of a local reaction of the molecule to control the inflammatory response elicited by gliadin. Gliadin is the sub fraction of gluten that acts as a toxin or poison in people with celiac disease; it causes an immune reaction, resulting in damage to the small intestine and an inability to digest and absorb nutrients necessary for health and growth (malabsorption).
    The findings, Anti-Inflammatory Effects of alpha-Melanocyte-Stimulating Hormone in Celiac Intestinal Mucosa, appear in the February 20, 2003 issue of NeuroImmunoModulation, the official journal of the International Society for Neuroimmunomodulation.
    Our research suggests that locally-produced alpha-MSH modulates inflammation and perhaps limits epithelial damage in patients with celiac disease, stated James M. Lipton, Ph.D., study investigator, chief scientific officer and director of Zengen. We are particularly excited by these findings as these data, coupled with abundant evidence of the anti-inflammatory and anti-infective activity of Zengens novel molecules based on alpha-MSH, further validate our research and development efforts in numerous areas including celiac disease. These positive results will be used to guide further advancements toward clinical use of the molecules.
    The study used human celiac mucosa cells in culture. Researchers collected duodenal biopsy pairs from 53 adult celiac patients (34 untreated patients and 19 celiac patients on a gluten-free diet) and 14 normal subjects and conducted three series of experiments in order to determine: (1) mucosal immunoreactivity for alpha-MSH and melanocortin receptors (MCRs), and gene expression of alpha-MSH precursor pro-opiomelanocortin and MCRs; (2) alpha-MSH and inflammatory cytokine production by duodenal specimens in vitro, and the influence of synthetic alpha-MSH on such cytokine production, and; (3) the influence of stimulation with gliadin on alpha-MSH and cytokine production in vitro and the effect of alpha-MSH on gliadin-stimulated cytokine production.
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    Zengens novel molecules were developed from more than 25 years of original research in the US, Europe and Asia on peptide molecules derived from alpha-Melanocyte-Stimulating Hormone (alpha-MSH). James Lipton, Ph.D., Zengens chief scientific officer, chairman of the scientific advisory board and director, and his collaborators first demonstrated that alpha-MSH possesses anti-inflammatory properties and uncovered the specific activity of the carboxy-terminal tripeptide region (C-terminal peptide) of the alpha-MSH peptide. These discoveries led to the development of Zengens proprietary peptide molecules, including CZEN 002, a synthetic octapeptide. Zengen is currently conducting phase I/II clinical trials with CZEN 002 in vaginitis.
    About Celiac Disease
    According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), celiac disease (celiac disease), also known as gluten intolerance, celiac sprue or gluten sensitive enteropathy, affects an estimated one in 250 Americans. Celiac disease is a condition in which there is a chronic reaction to proteins called glutens which causes destruction of the villi in the small intestine, with resulting malabsorption of nutrients. A genetic disease, it may appear at any time in the life of a person with a hereditary predisposition.
    Celiac disease is often misdiagnosed, symptoms are varied and there is no current medical treatment or cure. Patients who suffer from celiac disease currently have only one alternative -- adherence to a lifetime, gluten-free diet. If left untreated, celiac disease can lead to malabsorption, which, in turn, can lead to malnutrition. Celiac disease is especially serious in children and adolescents, who need adequate nutrition to develop properly. Further, people with celiac disease who dont maintain a strict, gluten-free diet have a greater chance of developing one of several forms of cancer, particularly intestinal lymphoma. Other long-term complications include anemia, diabetes mellitus, hypothyroidism, osteoporosis, seizures and peripheral neuropathy.
    About Zengen, Inc
    Zengen, Inc. is a biopharmaceutical company focused on discovering, developing and commercializing innovative products to treat and prevent infection and inflammation through application of its proprietary peptide technologies. Zengens novel molecules offer broad-based anti-infective and anti-inflammatory solutions for multiple diseases and disorders, ranging from yeast infection to transplantation, and have the potential to significantly alter the way these diseases are treated. For more information about Zengen, please visit www.zengen.com.
    Zengen, Inc. Forward-Looking Statement Disclaimer
    This announcement may contain, in addition to historical information, certain forward-looking statements that involve risks and uncertainties. Such statements reflect managements current views and are based on certain assumptions. Actual results could differ materially from those currently anticipated as a result of a number of factors. The company is developing several products for potential future marketing. There can be no assurance that such development efforts will succeed, that such products will receive required regulatory clearance or that, even if such regulatory clearance were received, such products would ultimately achieve commercial success.
    Source: Zengen, Inc.

    Scott Adams
    Celiac.com 12/27/2005 - The BioBalance Corp. (BioBalance), a wholly owned subsidiary of New York Health Care (OTC BB: BBAL), announced today that it has received approval to begin a small-scale clinical trial of its proprietary biotherapeutic agent, Probactrix, in the dietary management of patients with celiac disease, a chronic disorder of the gastrointestinal (GI) tract.
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    We are very excited to have approval to initiate this celiac study and to have provided a comprehensive response to FDA questions on our pouchitis IND, said Dennis ODonnell, BioBalances President and CEO.
    Celiac disease is an inherited condition where gluten proteins found in grains trigger an immune system attack on the lining of the small intestine. While celiac disease is rarely life threatening, it is a life altering disorder with symptoms such as diarrhea, fatigue, nausea and weight loss. Celiac is also linked to other autoimmune disorders and is now believed to lead to osteoporosis, anemia, infertility and cancer if left untreated. Diagnosis is often difficult because of the range of GI symptoms. A 2001 survey found that celiac patients in the U.S. suffer for 11 years on average before they are successfully diagnosed. Estimates from the NIH indicate that as many as one in 100 Americans have celiac disease, with significantly higher levels found in Finland, Italy, Ireland and Israel.
    Dr. Robert Hoerr, BioBalances Vice President of Medical & Regulatory Affairs, commented, Recent studies have identified a potential link between the overgrowth of pathogenic bacteria in the gastrointestinal tract and the symptoms of celiac disease. We are pleased to participate in this study, which will test the use of Probactrix as a means of modifying the bacterial flora in the GI tract and its impact on quality of life for these individuals.
    Contacts:
    Dennis ODonnell
    CEO
    The BioBalance Corp
    Tel: (212) 679-7778
    Fax: (212) 679-7774
    Stanley Wunderlich
    CEO
    Consulting For Strategic Growth
    Tel: (800) 625-2236
    Fax: (212)337-8089

    Roy Jamron
    Celiac.com 04/20/2008 - ActoGeniX is a recently formed Belgian company specializing in the development and use of genetically altered probiotic Lactococcus lactis bacteria designed to secrete and deliver therapeutic peptides and proteins to treat gastrointestinal disorders. Their product is called ActoBiotics™. Celiac disease is among the disorders ActoGeniX is currently investigating. Research has already shown efficacy in a celiac disease model where ActoBiotics™ continuously secrete small segments of gluten peptides to induce tolerance to gluten. Further research and trials are in the pipeline.
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    Technical information describing their product and initial research and development in detail is presented in the following patent application:  http://www.freepatentsonline.com/WO2007063075.html.


    Jefferson Adams
    Celiac.com 11/03/2008 - Blood testing for radioimmunoassay (RIA) tissue transglutaminase auto-antibodies (tTG-Abs) has proven to be a sensitive test for celiac disease follow-up. Recent studies have shown that RIA can accurately detect tTG-Abs in human saliva. However, not much is known about reliability of this method for monitoring the progress of celiac disease over time in patients who are attempting to follow a gluten-free diet.
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    The research team concluded that it is possible to measure salivary tTG-Abs with a high level of accuracy; both at initial diagnosis for celiac disease, and also while patients are following a gluten-free diet.
    This discovery means that doctors treating people with celiac disease might soon be able to use a simple saliva test to monitor the progress of their patients’ gluten-free diets. Such a development might take remove much of the guesswork for celiacs who are trying to follow a gluten-free diet, and would be particularly useful for patients who might be asymptomatic, or who are at risk for celiac-associated conditions.
    Aliment Pharmacol Ther.  2008; 28(3): 364-370.


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    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

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