Innovative mucus secretion stimulation for inflammation control in Inflammatory Bowel Disease

Descrizione del progetto

Aumentare la secrezione di muco per la remissione delle malattie infiammatorie intestinali

In condizioni di salute, lo strato di muco dell’intestino agisce come una barriera, tenendo i microbi lontani dal contatto diretto con le cellule intestinali e il sistema immunitario. Tuttavia, nelle malattie infiammatorie intestinali (IBD, inflammatory bowel disease), questa barriera è compromessa, il che permette ai microbi di penetrare lo strato di muco e di entrare in contatto con le cellule del rivestimento intestinale e con le cellule immunitarie sottostanti. Questo provoca un’infiammazione persistente e danni ai tessuti, alla base dei sintomi e della progressione della malattia infiammatoria intestinale. Il progetto MucusIBD, finanziato dal CER, sfrutta la scoperta secondo cui l’induzione di un eccesso di secrezione di muco intestinale nei topi protegge dalla colite. I ricercatori testeranno un acido biliare in modelli murini preclinici per indurre la produzione di muco e la remissione della malattia infiammatoria intestinale.

Obiettivo

Inflammatory bowel diseases (IBDs), such as Crohns disease and ulcerative colitis, are chronic, debilitating conditions affecting millions worldwide. There is currently no cure for IBD, only treatments aimed at inducing long lasting remission. These treatment options act mainly by inhibiting the patients immune system, leaving patients immunocompromised, and come with a high annual direct cost. Even with advanced treatment, most IBD patients will require surgery during their lifetimes. Thus, more affordable treatment option which are not focused on immune suppression are needed.

While the etiology of IBDs is not clear, it is thought that breakdown of gut barrier function is a major driver of chronic intestinal inflammation. Indeed, penetrance of luminal microbes into the mucus layer which covers the intestinal epithelium is a hallmark of IBDs. This penetrance and contact of microbes with the hosts immune system drives a proinflammatory response and prevents tissue healing. While performing our ERC-funded research project we found a way to induce excess intestinal mucus secretion in mice. We found this excess mucus secretion protected mice from development of colitis in a model of IBD. We also uncovered the mechanism which controls intestinal mucus secretion and discovered a cheap and reproducible way to pharmacologically induce excess mucus secretion using a bile acid.

Our goal is to determine whether pharmacologically inducing intestinal mucus production in preclinical mouse models of IBD can induce and sustain remission. The project's methodology encompasses preclinical trials utilizing three distinct mouse models to rigorously test the efficacy and safety of our innovation. A comprehensive market analysis, informed by stakeholders including healthcare professionals and patient advocacy groups, will guide the development process, ensuring the therapeutic approach meets the real-world needs of IBD patients.