rectal-organoid-morphology-analysis-roma-diagnostic-assay-cystic

Rectal Organoid Morphology Analysis (ROMA): A Diagnostic Assay in Cystic Fibrosis

Diagnosis of cystic fibrosis (CF) is not always straightforward, especially when sweat chloride concentration is intermediate and/or less than two ...

KU Leuven

University Hospitals Leuven

Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing  mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p<0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.

Rectal organoid morphology analysis (ROMA) as a promising diagnostic tool in cystic fibrosis.

Cystic fibrosis (CF) is a severe monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator () gene. Several types of CFTR modulators (correctors/potentiators) have been developed to overcome protein dysfunction associated with these mutations. CFTR modulator therapy is now available for the major CF-causing mutations; however, 10% of people with CF remain without causal treatments. By combining investigational and market-approved CFTR modulators, we aimed to maximise functional rescue of iva-, luma- and tezacaftor refractory mutants G85E and N1303K.

Article	Year
Rectal organoid morphology analysis (ROMA) as a promising diagnostic tool in cystic fibrosis. Thorax\| PubMed ID: 33859053	2021
Novel CFTR modulator combinations maximise rescue of G85E and N1303K in rectal organoids. ERJ open research\| PubMed ID: 35449760	2022

Senne Cuyx

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