Author Interviews, Gastrointestinal Disease / 03.11.2018

MedicalResearch.com Interview with: RedHill BiopharmaDror Ben-Asher Co-Founder, Chairman & CEO RedHill Biopharma Ltd. MedicalResearch.com: Your presentation at United European Gastroenterology Week (UEGW) covered top-line data from your recently completed Phase 3 study of RHB-104 in Crohn’s disease. Can you please briefly remind us of the background for this study and what results you previously announced? Response: Crohn's disease is a devastating gastrointestinal disorder that affects millions of people worldwide. Crohn's is a chronic relapsing disorder that plagues people throughout their lives with a variety of symptoms including severe abdominal pain, diarrhea, bleeding, bowel obstruction, fever and weight loss. The existing treatments for Crohn's disease leave a lot to be desired – they are only partially effective in the long-term control of Crohn's and are associated with serious side effects. In addition, the existing therapies only target treating the symptomatic inflammation associated with Crohn's. We began developing RHB-104 with the MAP hypothesis in mind, a theory that suggests Crohn's is caused by infection by a bacteria, Mycobacterium avium subspecies paratuberculosis (MAP), in susceptible patients. RHB-104 is a patent-protected orally-administered combination of three antibiotics (clarithromycin, clofazimine and rifabutin) in a single oral capsule that has demonstrated its potential to benefit Crohn's patients. When we announced top-line results from the MAP US study, our Phase 3 trial of RHB-104 in patients with moderate to severe Crohn's disease, we showed that RHB-104 demonstrated a significant clinical benefit to patients versus placebo control. Patients treated with RHB-104 showed significant increase in remission at 26-weeks post treatment initiation in addition to being generally safe and well tolerated. (more…)
Author Interviews, Gastrointestinal Disease, Global Health, Lancet / 18.10.2017

MedicalResearch.com Interview with: Gilaad Kaplan, MD, MPH, FRCPC Associate Professor CIHR New Investigator & AI-HS Population Health Investigator Co-Director, Environmental Health Research Group Snyder Institute for Chronic Diseases & Institute of Public Health Departments of Medicine & Community Health Sciences University of Calgary MedicalResearch.com: What is the background for this study? What are the main findings? Response: The aim of the study was to provide a global perspective on the epidemiology of the inflammatory bowel diseases in the 21st century. During the 20th century IBD was considered a disease of the Western world. At the turn of the 21st century, IBD has become a global disease with accelerating number of cases in the developing world as it transition towards a westernized society. (more…)
Author Interviews, Gastrointestinal Disease, Inflammation / 27.10.2016

MedicalResearch.com Interview with: Cheryl de Valliere, PhD University Hospital Zurich Division of Gastroenterology and Hepatology Zurich Switzerland and co-authors Gerhard Rogler, Jesus Cosin Roger, Pedro A. Ruiz MedicalResearch.com: What is the background for this study? Response: Inflammatory Bowel Disease (IBD), including ulcerative colitis and Crohn’s disease, gives rise to chronic relapsing inflammation of the gastrointestinal (GI) tract, resulting in a disruption of the epithelial barrier function and exacerbated innate and adaptive immune responses. One of the most important features under these inflammatory conditions is the presence of hypoxic areas where oxygen levels are lower than in normal tissue. It has been widely reported that the main transcription factor regulating cellular responses to hypoxia, hypoxia inducible factor (HIF)-1, is significantly induced in patients with IBD compared with healthy subjects. Furthermore, hypoxia is not only linked to inflammation, but also influences the local tissue pH, leading to an reduction of the pH in the inflamed mucosa compared with the non-inflamed one. A family of pH-sensing G-protein coupled receptors (GPCRs), including the receptor T-cell death-associated gene 8 (TDAG8) and the ovarian cancer G-protein coupled receptor 1 (OGR1 or GPR68), play an important role in physiological pH homeostasis. At low extracellular pH, second messenger signaling pathways are activated by protons binding to the histidine residues located on the extracellular region of the receptor. Recent studies have reported a link between IBD and this family of pH-sensing receptors. Indeed, TDAG8 has been identified as an IBD risk gene and we have previously reported an increased expression of OGR1 in patients with IBD compared with healthy subjects. To better understand the basic mucosal inflammatory mechanisms, and foster the development of new treatment options (e.g. pH receptor blockers and OGR1 antagonists) for chronic mucosal inflammatory diseases, we investigated the effects of hypoxia on pH-sensing OGR1 in the intestinal mucosa and associated cells. (more…)
Allergies, Author Interviews, BMJ, Gastrointestinal Disease / 16.12.2015

MedicalResearch.com Interview with: Meri K Tulic PhD Université de Nice Sophia-Antipolis Immune Tolerance Nice, France The International Inflammation 'in-FLAME' Network Worldwide Universities Network  Medical Research: What is the background for this study? What are the main findings? Dr. Tulic: We know that damaged epithelial gut barrier is a hallmark of gut inflammatory diseases including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). It has been long known that respiratory allergens such as house-dust mites (HDM) are the main causes of epithelial destruction in the lungs and initiation of allergic airway disease such as asthma. We set out to test whether  house-dust mites may also be present in the human gut and may contribute to intestinal barrier dysfunction. In this paper, we have shown that  house-dust mites is found in the gastrointestinal system of ~50% of all healthy subjects tested and it has detrimental effect on gut barrier function. The mechanisms include its direct destruction of tight-junction proteins which normally hold adjoining epithelial cells together, resulting in increased gut permeability. This process is driven by cysteine-proteases contained within the mite. In healthy individuals this effect is likely to be regulated by increased production of regulatory IL-10 (an anti-inflammatory mediator); our preliminary data indicate that a defect in regulatory responses may exist in IBS patients. (more…)
Author Interviews, Gluten, Pediatrics / 26.10.2015

MedicalResearch.com Interview with: Maria Ines Pinto Sanchez, MD MSc​ Post-doctoral Clinical ​ Research Fellow and Dr Elena Verdu, MD, PhD Farncombe Family Digestive Health Research Institute McMaster University Health Sciences Centre Hamilton, ON Medical Research: What is the background for this study? What are the main findings? Response: Celiac disease is a condition caused by ingestion of gluten in people with genetic predisposition, in which the finger like projections of the intestinal lining are damaged by inflammation. The “celiac” genes are necessary, but not sufficient, to develop celiac disease. For this reason, it is believed that additional factors could influence the risk of a predisposed child to develop celiac disease. Some studies have indeed suggested that the ideal time for the introduction of gluten to the diet would fall between the 4th and 6th month of life, when gluten should be introduced in “small quantities” and progressively, while maintaining breastfeeding whenever possible. The Nutrition Committee of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition recommended avoiding the introduction of gluten before 4 months and after 7 months of age in an attempt to prevent celiac disease. However, not all clinical studies reached this conclusion and we therefore conducted an updated analysis of the literature published on this subject to evaluate the relationship between time and amount of gluten introduction, breastfeeding and the risk of developing celiac disease. Our systematic analysis revealed that based on the studies published to date there is no strong support that early gluten introduction to an infant’s diet increases the chances to develop celiac disease or that breastfeeding specifically protects from it. (more…)
Author Interviews, Circadian Rhythm, Gastrointestinal Disease, Sugar / 23.05.2014

Dr. Robin Voigt PhD Department of Internal Medicine Division of Gastroenterology Rush University Medical Center Chicago, IllinoisMedicalResearch.com Interview with: Dr. Robin Voigt PhD Department of Internal Medicine Division of Gastroenterology Rush University Medical Center Chicago, Illinois MedicalResearch: What are the main findings of the study?  Dr. Voigt: We found that chronic circadian rhythm disruption has no effect on the intestinal microbiota when mice are fed a standard chow diet but when combined with a high-fat, high-sugar diet circadian rhythm disruption results in intestinal dysbiosis and an increase in pro-inflammatory bacteria. (more…)