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Project

Study on new treatment options for irritable bowel syndrome

Abdominal pain accompanied by a change in bowel habit, in the absence of an organic cause, is the main diagnostic criterion for irritable bowel syndrome (IBS). The condition has an estimated prevalence of up to 18% in the Western population and has a significant economic impact with up to 12% of IBS patients having to stop work completely. Remarkably, treatment of this disorder is rather disappointing and restricted to symptomatic treatment aiming to normalize stool pattern. This approach however fails to relieve abdominal pain resulting in disappointment for both patients and treating physicians. Recently we discovered that food-antigen induced mast cell activation and histamine 1 receptor mediated sensitization of nociceptors play a key role in IBS (Aguilera-Lizarraga Nature 2021). Of interest, in a pilot study of 55 IBS patients, we also demonstrated that targeting this mechanism with the histamine 1 receptor antagonist ebastine significantly improved abdominal pain and symptomatic relief. The therapeutic response (i.e. at least considerable relief) was 46% for the ebastine group compared to 13% for patients treated with placebo, yielding a therapeutic gain of more than 30% (Wouters et al., Gastroenterol 2016). In my PhD, I will perform a large comparative clinical study comparing the effect of ebastine with that of the spasmolytic mebeverine in 200 IBS patients. In addition, I will search for new targets based on ongoing preclinical studies in our lab. One target that I will further explore is GPR18. We previously showed that resolvin D2, acting on GPR18, potently reverses and prevents sensitization of dorsal root ganglion neurons (Perna et al., Gut 2021). In my thesis, I will evaluate the effect of GPR18 agonists as potential new treatment for IBS. Taken together, in my thesis, I will further validate histamine 1 receptor antagonism as new treatment for IBS and will explore GPR18 agonists as potential new approach to improve abdominal pain.

Date:2 Jan 2023 →  Today
Keywords:Irritable bowel syndrome
Disciplines:Gastro-enterology
Project type:PhD project