Small details, intriguing discoveries, and new insights that help us better understand cystic fibrosis and the mechanisms behind the CFTR protein, the key protein behind the disease.
These findings not only expand our scientific knowledge but also offer concrete ideas for developing new therapeutic strategies and enhancing the effectiveness of existing treatments. From the discovery of natural molecules that can modulate CFTR to innovative techniques that allow scientists to observe the protein “in action” inside living cells, each story represents a step forward toward more precise and personalized therapies.

In the following sections, we will take you through these five stories, explaining why they matter and what they could mean for people living with cystic fibrosis.

1. Using “molecular paint” to map CFTR

Imagine trying to study a highly complex machine that not only has an intricate structure, but also constantly changes shape while it is working. Observing it in a static state is not enough to truly understand how it functions. This is similar to the challenge researchers face when studying the CFTR protein, whose malfunction causes cystic fibrosis.

To overcome this limitation, a recent study (this one) used an innovative method called Covalent Protein Painting (CPP), which allows scientists to literally “paint” the surface of the protein inside living cells. A chemical probe binds only to the regions that are exposed at a given moment, leaving hidden areas unmarked. By seeing which parts are labeled and which are not, researchers can map how CFTR folds, shifts, and opens or closes to carry out its function—essentially creating a dynamic map of the protein in its natural environment.

This approach revealed a previously unknown mechanism for how the CFTR channel opens and highlighted an “immature” form of the protein that can interfere with its proper function, helping explain the effects of some complex mutations. CPP also allowed researchers to examine mutations such as N1303K, which currently respond only partially to available CFTR modulators. In these cases, the protein adopts less stable shapes, making it harder for drugs to work effectively.

Understanding these details provides a crucial foundation for developing future therapies designed to stabilize the protein and target even the most challenging variants.

2. Enhancing CFTR with nature-inspired molecules

This study has drawn new attention to kinetin, a plant-derived molecule, and to a more potent analogue known as RECTAS, for their potential role in improving CFTR gene function in cystic fibrosis. In many people with CF, small errors in the way cells “read” DNA—known as splicing defects—can lead to the production of incomplete or poorly functioning CFTR protein.

Researchers found that kinetin and RECTAS help cells interpret genetic instructions more accurately, increasing the production of functional CFTR protein. In patient-derived cells, RECTAS was able to quadruple the amount of functional CFTR. Importantly, these compounds are not meant to replace existing therapies but to enhance their effectiveness by making the genetic message clearer for the cell. The concept is similar to turning up the volume on a weak radio signal: by amplifying and clarifying the correct messages, these molecules may allow current treatments to work more effectively.

The study thus represents a further step toward more targeted and personalized therapies, particularly for those who currently have limited treatment options, and highlights the ongoing value of research in finding new solutions for CF—sometimes by leveraging mechanisms already present in nature.

3. A new balance for lungs and infections

The lungs of people with cystic fibrosis can be thought of as a clogged filter, where stubborn bacteria like Pseudomonas aeruginosa and Staphylococcus aureus get trapped, leading to recurrent infections that worsen lung function and cause chronic complications.

This study of over 8,000 people across Europe examined why some infections disappear after treatment with elexacaftor/tezacaftor/ivacaftor (ETI, Kaftrio, Trikafta) while others persist. The researchers found that older age and already damaged lungs increase the likelihood that bacteria remain. Still, even those with chronic infections experienced improvements in breathing and quality of life, showing that the therapy can “clear the filter,” reducing the impact of infections and supporting better overall lung function.

4. Inflammation as an Unexpected Ally in Cystic Fibrosis

One of the most difficult challenges in cystic fibrosis involves people with nonsense mutations—genetic changes that interrupt the production of the CFTR protein before it is fully made. These mutations are difficult to treat because CFTR modulator require a complete protein to work. One promising approach for stop mutations relies on readthrough compounds, which help the cell bypass the premature stop signal and continue producing the CFTR protein. Until now, however, their effects have been modest.

This study points to a potential breakthrough. The researchers found that inflammation, a defining feature of affected lungs, can significantly boost the effectiveness of readthrough therapies. They tested three compounds, including ELX-02 and CC-90009, in airway cells from people with cystic fibrosis carrying the G542X and W1282X mutations. Without additional stimuli, CFTR function improved only slightly. When inflammatory signals such as the cytokines IL-4 or IL-17A were added, CFTR activity increased by up to 15-fold.
In this context, inflammation appears to prime the cells, making them more responsive to the readthrough process that allows full-length CFTR protein to be produced.

These findings suggest that future therapies may be more effective precisely in inflamed lungs, and that drug performance depends not only on the compounds themselves, but also on the biological environment in which they act—opening new directions for personalized treatment in cystic fibrosis.

5. Diabetes in CF impacts lungs as well as blood sugar

Cystic fibrosis–related diabetes (CFRD) is not just a problem of blood sugar—it also affects the lungs. A study found that people with CFRD have more inflamed airway mucus and a different mix of proteins, many linked to inflammation. Mucus can be thought of as a snapshot of the lungs: analyzing which proteins are present and in what amounts is a bit like reading the ingredients list on a product to understand how it’s made.

These differences don’t seem to depend only on the severity of lung disease. Even among people with similar lung function, those with diabetes showed more irritated airways. CFRD can therefore actively contribute to worsening lung health, highlighting the need for treatments that address both metabolism and respiratory health together.