Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which impair the function of the protein of the same name, essential for maintaining proper salt and fluid balance in the airways.

In recent years, CFTR modulators such as Kaftrio have transformed the lives of many people with CF, especially those who carry at least one copy of the F508del mutation. Yet not everyone benefits equally, and almost one-third of Italian patients have rarer CFTR variants for which the effectiveness of current modulators remains uncertain. The landscape will soon become even more challenging: alongside Kaftrio, the new modulator Alyftrek, is about to enter clinical use. For those with rare CFTR variants, clinicians will soon face a challenging decision between two therapies, with no comparative data to show which is more effective for these rare mutations.
This makes it crucial to have tools that can help predict which treatment is likely to work best for each individual patient.

Theratyping addresses this need: it consists of testing drugs directly on a patient’s own cells, obtained through a simple nasal brushing. These cells retain the person’s genetic characteristics and make it possible to observe in the laboratory whether, and to what extent, the CFTR protein resumes functioning when treated with a modulator. While these tests cannot predict everything that will happen in real life, they provide valuable insight: they show whether the drug is truly correcting the underlying defect of the disease.

NEXT-CF provides clinicians with an ex vivo theratyping service that helps identify the most suitable treatment for people with CF who carry rare CFTR variants, anticipate which individuals are unlikely to respond to available modulators, and build a valuable biobank of cellular models for testing future therapies.

The UOC Genetica Medica, Unit, at the IRCCS G. Gaslini Institute of Genoa, is one of the few European centers recognized by the ECFS Clinical Trial Network for performing these tests with standardized, validated methods. It also serves as a training hub for other laboratories across Europe. Its extensive experience and high methodological standards ensure that each NEXT-CF test provides clinicians with clear, actionable information to guide treatment decisions.