A personalized assay for cystic fibrosis

An analytical test to quantify the function of CFTR, a molecular receptor whose dysfunction causes cystic fibrosis, is reported in a study published this week in Nature Medicine. This fast and robust test uses ‘organoids’ derived from patients with cystic fibrosis to facilitate diagnosis, assess drug response and optimize treatment for each individual.

Few tools exist to screen for efficacy of drugs restoring the function of CFTR and the response of cystic fibrosis patients to the drugs.Even for those with the same mutations, treatment can be variable, which poses a challenge for patients and physicians.

Jeffrey Beekman and his colleagues adapt a technique that uses intestinal stem cell organoids to grow tissues from cystic fibrosis individuals with various mutations in the CFTR gene.By using a compound called forskolin, the authors were able to induce swelling of the organoids, which are reduced or lost in patients with CFTR mutations. Treatment of the organoids with drugs that increase CFTR function re-introduces this swelling, which can be quantified to assess restoration of receptor function on an individual basis.

The authors maintain that this quick in vitro assay can easily generate large amounts of cellular data from patients with different clinical phenotypes of cystic fibrosis and may be useful to predict patient drug response, which was found to vary even among individuals carrying the same CFTR mutation.

doi: 10.1038/nm.3201

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