Peter van Mourik

149 Personalized treatment of CF using rectal organoids Figure 1 - Significant correlation between individual in vitro organoid response and in vivo change in ppFEV 1 and SCC. (a) Confocal images of the FIS of organoids with an F508del/S1251N mutation. Images are taken 0 and 60 minutes after adding DMSO, genistein plus curcumin and ivacaftor (VX-770) in combination with forskolin. (b) AUC of the swelling of organoids after measuring for 60 minutes. The graph shows responses after adding eight different concentrations of forskolin in combination with either DMSO or a CFTR modulating treatment. Mean, ± SD (c,d) Pearson correlations between response of the organoids of an individual patient upon CFTR modulating treatment in combination with 0.128 μM Forskolin and the in vivo response (change in ppFEV 1 and change in SCC) of the same patient to the same treatment for patients who had a ppFEV 1 ≥40% and ≤90% before the start of treatment. (e) Pearson correlation between change in ppFEV 1 and change in SCC of individual patients upon a CFTR modulating treatment for patients who had a ppFEV 1 ≥40% and ≤90% before the start of treatment. (f,g) Pearson correlations between response of the organoids of an individual patient upon CFTR modulating treatment in combination with 0.128 μM Forskolin and the in vivo response (change in ppFEV 1 and change in SCC) of the same patient to the same treatment for patients who had a ppFEV 1 <40% or >90% before the start of treatment. (h) Pearson correlation between change in ppFEV1 and change in SCC of individual patients upon a CFTR modulating treatment for patients who had a ppFEV 1 <40% or >90% before the start of treatment. (i,j) Pearson correlations between response of the organoids of an individual patient upon CFTR modulating treatment in combination with 0.128 μM Forskolin and the in vivo response (change in ppFEV1 and change in SCC) of the same patient to the same treatment for all patients that received treatment. (k) Pearson correlation between change in ppFEV1 and change in SCC of individual patients upon a CFTR modulating treatment for all patients that received treatment. See also Figure S1, S2 and Table S1. 7