Il problema affrontato dai ricercatori è stato verificare se gli organoidi intestinali derivati da pazienti FC rispondano tramite rigonfiamento (indicativo di funzionamento di CFTR, perché il rigonfiamento è dovuto a secrezione di liquido CFTR-dipendente entro l’organulo sferico) al trattamento con plasma contenente farmaci modulatori di CFTR mutata. Gli organoidi FC sono stati trattati con plasma di pazienti in terapia con i nuovi farmaci, in particolare sono stati usati organoidi da soggetti omozigoti F508del in terapia con Lumacafor/Ivacaftor. È stato visto che con l’esposizione al plasma dei pazienti sensibili alla terapia con modulatori l’organoide si rigonfia, indicando il funzionamento di CFTR. Non è stato possibile invece stabilire una correlazione fra il rigonfiamento dell’organoide e il livello di cloro al test del sudore e il livello di funzionalità respiratoria dei pazienti. Debbono essere proseguiti gli studi per capire se esista una correlazione fra la risposta dell’organoide al farmaco presente nel plasma e questi altri indicatori biologici e clinici.
The objective of the project was to investigate the variability of response to CFTR modulators among CF patients and to inquire if this variability correlates with the swelling response of human intestinal organoids exposed to plasma drugs levels in patients receiving this therapy. Active drugs were analyzed on specific CFTR gene mutations in the plasma of CF patients during therapy, in particular, Ivacaftor / Lumacaftor (VX-770 / VX-809, Orkambi). With the known dose of drug added to the human plasma laboratory of non-CF volunteers, the method was set up. The swelling effect on the CF organoids induced by non-CF plasma level drug was compared with the plasma effect of CF patients during treatment. Patients with circulating levels of Ivacaftor/ Lumacaftor have been identified as effective in inducing the swelling of the CF organoids. But no clear correlation was identified with patients’ chlorine levels at the sweat test nor with functional respiratory tests. CF plasma patients treated with CFTR modulators can be tested to discover if intestinal organoid responds to the treatment; further research is needed to understand if the effect of the drug on the organoid correlates with the effect on the patient clinical picture.
– Caldrer S, Baruzzi A, Vercellone S et al. “Intestinal epithelial organoids contribute to supporting drug development and diagnosis” 17th Scientific Meeting “Organoids as models for disease and treatment in CF” September 21st + 22nd 2017 Schloss Waldhausen/Mainz”
– Caldrer S, Baruzzi A, Vercellone S et al. “A collection of intestinal epithelial organoids to support the development of drugs and diagnostic in cystic fibrosis by combining CFTR functional tests in personalized medicine” ECFC Basic Science Conference 2018, 21 -24 March 2018, Loutraki Korinthias, Greece
– Baruzzi A, Caldrer S, Lecca M et al. “CORVO: a software tool for computing volume of complex biological structures in medical images and videos” SIAM Conference on Imaging Science, Bologna, June 5-8, 2018
– Lecca P, Lecca M, Caldrer S et al. “Computing volumes of organoids from 3D confocal acquisition with CORVO” North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, USA
– Lecca P, Lecca M, Caldrer S et al. “Computing volumes of organoids from 3D confocal acquisition with CORVO” North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, USA
– Rescigno F, Farinazzo A, Esposito V et al. “CFTR-dependent bicarbonate transport in human rectal biopsies carrying CFTR variants” North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, USA
