Gastroenterology - Irritable Bowel Syndrome

IRRITABLE BOWEL SYNDROME

In the last decade, scientific and medical evidence has clearly demonstrated a crucial role of mast cell activation in the pathophysiology of IBS. Several studies have clearly shown that estimated 75% of patients with Irritable Bowel Syndrome (IBS-Diarrhea / Pain) have abnormal activated mast cells – and partially increased number of mast cells – in their gastrointestinal tract. The abnormal activated mast cells are directly related to visceral hypersensitivity, abdominal pain, diarrhea frequency and further IBS symptoms. Patients fulfilling criteria for therapy-resistant IBS are commonly found to suffer from mast cell activation disease.

The activation of mast cells participates in multiple pathophysiological processes of IBS (see graphic):

  1. Barrier disruption: regulating epithelial permeability via acting on tight junction.
  2. Secretion disorder: regulating epithelial water and ion transport.
  3. Inflammation: regulating blood flow and endothelial functions, as well as immunomodulation, inflammation, and defense against microbes.
  4. Dysmotility: regulating intestinal peristalsis.
  5. Visceral pain: regulating function of visceral afferent and sensation via neuro-immune mechanisms.

So far, despite immense research therapeutic options have not yet shown significant progress since they target symptoms but not the underlying root cause leading to an urgent need for new therapies targeting mast cells in IBS. Our novel mast cell therapy could for the first-time provide a cause-related and highly effective therapy for IBS.

IBS has an estimated prevalence of 412 million patients worldwide with an estimated 34 million diagnosed patients in the major markets.

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Scientific Sources
  1. T. Frieling, K. Meis, U.W. Kolck, J. Homann, A. Hülsdonk, U. Haars, H.-J. Hertfelder, J. Oldenburg, H. Seidel, G. J. Molderings, Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome, Z Gastroenterol 2011; 49: 191–194
  2. Guy E. Boeckxstaens, MD, PhD, Advances in IBS – The emerging role of mast cells, Gastroenterology & Hepatology Volume 14, Issue 4 April 2018
  3. Philpott H., Gibson P., Thien F., Irritable bowel syndrome – An inflammatory disease involving mast cells, Asia Pac Allergy 2011;1:36-42
  4. Gerald J. Holtmann, Alexander C Ford, Nicholas J Talley, Pathophysiology of irritable bowel syndrome, Lancet Gastroenterol Hepatol 2016; 1: 133–46
  5. Lei Zhang, Jun Song, and Xiaohua Hou, Mast cells and irritable bowel syndrome: from the bench to the bedside, J Neurogastroenterol Motil, Vol. 22 No. 2 April, 2016
  6. Mira M Wouters, Maria Vicario, Javier Santos, the role of mast cells in functional GI disorders, Gut 2016;65:155–168.
  7. Hyuk Yoon, mast cell may be the master key to solve the mystery of pathogenesis of irritable bowel syndrome, Gut and Liver, Vol. 10, No. 3, May 2016, pp. 325-326
  8. Stephan C. Bischoff, Mast cells in gastrointestinal disorders, Eur J Pharmacol, 2016
  9. Raithel, M., Molderings J G. et al, Reizdarm und Mastzellen, Basiswissen Allergie 03-2015
  10. Beatriz Lobo et al, Downregulation of mucosal mast cell activation and immune response in diarrhoea-irritable bowel syndrome by oral disodium cromoglycate: A pilot study, United European Gastroenterology Journal 0(0) 1–11, 2017