Cheating or Not Responding to the Gluten-Free Diet? New Test Helps Doctors to Tell the Difference

woman-eating-cookieA study by Dr. Francisco Leon, MD, PhD and CEO and Chief Medical Officer of Celimmune LLC evaluated a new method for assessing adherence to the gluten-free diet (GFD) and its correlation with mucosal damage by measuring gluten immunogenic peptides (GIP) in urine.  The method was developed by the diagnostics company Biomedal S.L. of Seville, Spain, which also sponsored the study, coordinated by researchers of the University of Seville, Spain. Pharmiweb Press Release, December 9, 2015

Why develop such a test?

  • Such a test would be extremely valuable for researchers monitoring celiac disease patients for gluten-free diet adherence to ensure the accuracy and interpretability of clinical trials evaluating the efficacy of potential non-dietary treatments.
  • Gastroenterologists could use the urine-based test to assist in the diagnosis and assessment of non-responsive celiac disease and refractory celiac disease.
  • The test would enable the diagnosis of refractory celiac disease type II, a serious disease which cannot be accurately diagnosed until the consumption of gluten is absolutely ruled out.

How was the study performed?

  • In the study, Dr. Leon and colleagues aimed to use consumption of gluten as a biomarker of celiac disease activity.
  • They collected urine samples from 76 healthy volunteers and 58 patients with celiac disease, and tested the samples for GIP.

Results

  • GIP was detected in urine samples in a positive correlation with the amount of gluten ingested, as early as 4 to 6 hours after gluten consumption, and remained detectable for 1 to 2 days.
  • The test showed high sensitivity, with as few as 50 mg of gluten, the lowest amount known to cause mucosal damage in celiac disease patients, detected in urine (Catassi et al, 2007).
  • 48% of adults (N=27) and 45% of children (N=31) with celiac disease on a long-term GFD consumed gluten and had detectable GIP in their urine samples.
  • Retrospective analysis of duodenal biopsies in 25 celiac disease patients revealed that 89% of subjects with normal mucosa had undetectable GIP in urine samples, while all patients with mucosal damage had detectable GIP in their urine.
  • While the analysis detected recent consumption of gluten, for up to 1-2 days, the levels of quantifiable urinary gluten showed a statistically significant correlation (p=0.0005, r=0.75) with the severity of mucosal damage, considered to be an outcome of sustained gluten consumption over weeks or months.

Applications, according to Dr. Leon

  • “A short-term, non-invasive urine-based gluten monitoring test would complement the existing longer term stool-based test and be a breakthrough for the entire celiac community.
  • The test would be extremely valuable for researchers monitoring celiac disease patients for gluten-free diet adherence to ensure the accuracy and interpretability of clinical trials evaluating the efficacy of potential non-dietary treatments.
  • In addition, gastroenterologists could use the urine-based test to assist in the diagnosis and assessment of non-responsive celiac disease and refractory celiac disease.
  • In particular, the test will enable the diagnosis of refractory celiac disease type II, a serious disease which cannot be accurately diagnosed until the consumption of gluten is absolutely ruled out.”

Next steps

  • “Celimmune’s upcoming Phase 2 clinical trial of AMG 714 in refractory celiac disease Type II will be the first experimental non-dietary therapeutic study in celiac disease to include the use of a non-invasive gluten monitoring test to ensure patient adherence to the gluten-free diet.
  • Understanding whether a patient is consuming gluten is essential for the success of our rapid go/no-go studies and, in fact, any study conducted in celiac disease. Our study will be using the stool-based test, which is already available in the E.U. and we will include the experimental urine-based test to continue supporting the development of this immunological assay.”

Ángel Cebolla, Ph.D., CEO of Biomedal S.L. comments

  • “The lack of adherence to a gluten free diet in celiac disease patients may cause long-term complications, such as osteoporosis, increased risk of bone fracture or lymphomas.
  • Many of these patients consume gluten because they relax their compliance to a GFD diet, or have unintentional contamination through food, oral medications or vitamins.
  • Our non-invasive and easy to use urine-based test could help patients check their dietary compliance and precisely identify contamination with gluten, giving them the information they need to avoid gluten, if possible.
  • This test represents a significant advance that opens up new possibilities for the gastroenterologist to more effectively treat this disease, assess GFD compliance and improve the quality of life of patients with celiac disease.
  • We are currently collaborating with clinical laboratory companies to bring our first generation, E.U. cleared, stool-based test method to the U.S.”

Refractive celiac diseaseAbout Celiac Disease and Refractory Celiac Disease

Celiac disease is a chronic hereditary systemic autoimmune and inflammatory disease triggered by gluten consumption. Celiac disease is characterized by damage to the lining of the small intestine, causing gastrointestinal dysfunction and debilitating symptoms. Nutritional malabsorption can lead to a failure to thrive in children and anemia and osteopenia in adults. Over the course of a life time, untreated or poorly managed celiac disease is often associated with deteriorating general health, multiple serious intestinal and extra-intestinal medical complications, and increased morbidity and mortality. Currently 1% of Western and 0.5% of Asian populations suffer from celiac disease and diagnosed prevalence is expected to increase dramatically with improved diagnostic tools and clinical awareness.

Refractory celiac disease (RCD), also known as refractory sprue, is a rare but specific complication of celiac disease, which is believed to appear after many years of inadvertent or intentional exposure to gluten. RCD is defined as persistent or recurrent intestinal atrophy and symptoms despite following a strict gluten-free diet for at least 6-12 months, and in the presence of aberrant intraepithelial lymphocytes, unique immune cells found in the lining of the small intestines.

CelimmuneAbout Celimmune

Celimmune LLC is a clinical development-stage immunotherapy company focused on treating and preventing autoimmune diseases and is headquartered in Bethesda, Maryland. Celimmune will initially focus its distinctive core competence in translational medicine, immunotherapy clinical development and commercialization on combating celiac disease and other serious autoimmune diseases. Celimmune has an exclusive licensing agreement with Amgen to develop, manufacture and commercialize AMG 714, a Phase 2-stage anti-IL-15 monoclonal antibody, for the treatment of diet non-responsive celiac disease and refractory celiac disease Type II, an in situ small bowel T cell lymphoma. For more information on Celimmune, please visit www.celimmune.com.

ivydal biomedalAbout Biomedal S.L.

Biomedal S.L. is a privately held biotechnology company based in Sevilla, Spain, whose mission is to develop and commercialize new technologies, services and products for research, bioindustry and diagnostics. The company develops its activities in two areas: Biomedal Life Sciences and Biomedal Diagnostics. Biomedal Life Science is devoted to the development and commercialization of products and services for life sciences research, and technology for industrial bioprocesses. Biomedal Diagnostics offers innovative products and services related to food safety and health. For more information on Biomedal, please visit ivydal.biomedal.com.

About Dr Francisco Leon, CEO and Chief Medical Officer of Celimmune

Dr. Leon is a clinical immunologist and drug developer with a strong passion for serving the celiac disease community. Francisco got to the celiac disease field via an unusual path, by studying structural immunology and peptide binding to HLA in 1993-94 in Norway, while taking a year off from his MD studies in Madrid. Armed with an interest in the molecular mechanisms of celiac disease, Francisco went back to earn his MD and then studied over 400 celiac disease patients for his PhD thesis on the autoimmune condition. His work contributed to some of today’s common celiac disease diagnostic tests, such as the anti-transglutaminase ELISA and the flow cytometry of intestinal lymphocytes. Francisco then moved the US in late 2001 to continue his research at NIH, where he was informed that “there’s almost no celiac disease in the US, it’s a European thing” and was encouraged to work in other autoimmune diseases. At the conclusion of his fellowship in 2004 and after attending the NIH Consensus Conference on Celiac Disease, when the US celiac disease situation was finally acknowledged, Francisco joined the pharmaceutical industry to improve patients’ lives.

Francisco’s industry career has been a cycle of: 1) Try to get Big Pharma to work in the celiac disease field, while developing drugs for other important diseases; 2) Leaving to do celiac disease research himself in a small company; 3) Repeat.  As a result, Francisco has led teams in Big Pharma (Bristol Myers, MedImmune/Astra Zeneca, Janssen/Johnson & Johnson) and in two celiac disease start-ups (Alba Therapeutics and his current company, Celimmune, co-founded with Ashleigh Palmer after leaving J&J this past February).  Francisco has been involved in more trials than any other industry clinician. He also continues to develop celiac disease diagnostics, most recently contributing to the development of the first gluten-free diet monitoring tool.

Francisco is also Adjunct Research Associate Professor of Medicine at Jefferson Medical College (Philadelphia) and has authored or co-authored over 75 peer-reviewed articles and book chapters as well as several patents. Excerpted from CeliacCentral.org

References

1.  Moreno ML, et al. Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut 2015;0:1-8.
2.  Catassi C, Fabiani E, Iacono G, et al. A prospective, double blind, placebo controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007;85:160-6.

To view the original version on PR Newswire, visit: http://www.prnewswire.com/news-releases/celimmune-co-authors-study-demonstrating-gluten-peptides-in-urine-correlate-with-mucosal-damage-in-celiac-disease-300190226.html

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