P071 Evaluation of CFTR modulator efficacy by rectal organoid morphology analysis (ROMA) indexes

Objectives: In patient-derived rectal organoids (PDRO), CFTR modulator efficacy can be evaluated in the forskolin-induced swelling (FIS) assay. this assay, PDRO response to acute stimulation with forskolin (Fsk) and potentiator(s) is quantified as a measure of restoration function after incubation corrector(s). However, high residual and/or (eg. potentiator effect elexacaftor), may swell already during step, before any FIS measurements. The magnitude underestimated these cases. Comparison non-CF therefore also not informative. Rectal organoid morphology analysis (ROMA) indexes have been shown previously (Cuyx Thorax 2021) discriminate between from subjects without CF. Methods: were cultured for 71 ranging CF function. incubated different combinations tezacaftor, elexacaftor, ivacaftor, Fsk; acutely stimulated Fsk VX-770. ROMA calculated all conditions time points, evaluate shift range towards over time. Results: reflect changes according genotype treatment. Non-CF regardless treatment, do non-rescuable range. F508del homozygous intermediate teza-/ivacaftor, elexa-/teza-/ivacaftor. capture which no measurement performed Conclusion: provide additional information complementing example response, allowing expansion dynamic testing PDRO.