Background & Rationale Working Group
Individual CFTR function and changes thereof after starting CFTR modulator treatment play a dominant role in individual disease expression and progression. Currently, CFTR genotyping and complementary characterization of in vitro, ex vivo and in vivo biomarkers of CFTR function are available to help understand how CFTR genetic diversity impacts CFTR function and clinical phenotype. Biomarkers of CFTR function measurements can be particularly relevant in the context of rare CFTR variants, either in the context of disease outcomes or definition of therapeutic impact. Ex vivo biomarkers of CFTR function are CFTR function measurements in in vitro cultured patient-derived cells that can enable relatively precise estimations of individual CFTR function under native or CFTR modulator conditions.
Importantly, these biomarkers can uniquely enable large scale pretesting of CFTR modulators before clinical introduction but depend on well trained staff and expensive equipment and are relatively labor-intensive to execute. This is highly relevant as multiple profoundly effective CFTR modulator treatments are becoming available for people with CF (pwCF), and development of novel CFTR modulator treatments are anticipated. We believe robust biomarkers can play an important role in predicting the magnitude of disease for pwCF and enable optimal selection of therapy for the individual person.
Here, patient-derived intestinal organoid (PDIO) cultures can serve as a valuable in vitro platform for individualized CFTR function assessment. Therefore, there is a need to build a collaborative network of researchers, clinicians and industry partners to accelerate the translation of patient-derived organoids based CF research into clinical practice.