FFC#5/2020

Intestinal organoids for assessment and pharmacological correction of abnormalities in fluid transport and anion currents in patients affected by pancreatitis

FFC#5/2020

Intestinal organoids for assessment and pharmacological correction of abnormalities in fluid transport and anion currents in patients affected by pancreatitis

PRINCIPAL INVESTIGATOR

Luca Frulloni (Università degli Studi di Verona, Dip. di Medicina, Div. Gastroenterologia)

Partner

Hugo De Jonge (Erasmus University Medical Center); Vincenzina Lucidi (Ospedale Pediatrico Bambino Gesù, Centro Fibrosi Cistica)

RESEARCHERS

8

CATEGORY

AREA 2 Personalized therapies

DURATION

1 year

GOAL

€ 43.000 €

RESULTS

In this project, researchers evaluated bicarbonate transport in intestinal biopsies and organoids derived from patients with recurrent idiopathic pancreatitis (PIC) with at least one allele of the mutated CFTR gene. Thanks to the use of the intestinal organoid culture technique, the researchers developed colonoids, or primary cultures from intestinal mucosal cells from 24 patients. These experimental models allowed the research team to study the recovery of CFTR functionality evaluating the transport of the bicarbonate ion, which could be specifically altered in some of these subjects. In fact, bicarbonate is essential for the proper action of the mucus and for the correct activation of pancreatic enzymes which, if not properly working, can cause episodes of pancreatitis. Given the complexity of the analyzes, the results are still being collected and processed. At the moment, about half of the patients have been analyzed in the laboratory of Partner Prof. De Jonge in Rotterdam*. The researchers expect to complete the analysis within the end of 2022. Preliminary data also indicate that the transport of chlorine and bicarbonate ions is increased in cells treated with Kaftrio; further studies to confirm this data are still ongoing. The experiments might provide interesting information about specific cases that could benefit from the use of therapies already available to prevent dangerous episodes of pancreatitis in cystic fibrosis patients.

*Professor Hugo De Jonge passed away on june 2022.

OTHER RESULTS

FFC#2/2022

Characterization of CFTR modulators mechanism of action via Photo-Affinity Labeling (PAL) approach

FFC#6/2022

Search for drug combinations killing Mycobacterium abscessus in cystic fibrosis

FFC#1/2021

Multiomics exploration of the CF primary bronchial epithelium lipidome and its role on CFTR rescue