Kaftrio (ETI), a drug obtained from the combination of two correctors (elexacaftor and tezacaftor) and an enhancer (ivacaftor), is currently the main treatment for a large number of people with cystic fibrosis (CF). Initially indicated for patients with at least one F508del mutation in the CFTR gene, in 2025 the EMA and in early 2026 the AIFA also authorized its use in carriers of at least one non-class I mutation.
Despite having provided significant results, this therapy can be further improved.

This project aimed to identify molecules capable of activating Heat Shock Proteins (HSPs), chaperone proteins that facilitate the correct three-dimensional folding of other proteins. The hypothesis underlying the study is that the activation of HSPs may enhance the effectiveness of correctors in restoring the function of the CFTR protein with the F508del mutation. 

A screening was conducted for proteins capable of activating Heat Shock Proteins within cells. This screening was initially conducted on cell lines derived from human bronchial epithelium. The molecules active in cell models were tested on primary cells derived from people with CF and with the F508del mutation on both copies of CFTR, in collaboration with CFaCore and the Primary Cultures Service.
Among the molecules tested, two proved effective in enhancing the effect of correctors in the cell lines used.
Furthermore, one of the two drugs, already in use for another disease, has also proved effective in primary cells with F508del, although its mechanism of action appears to be different from that hypothesized and does not involve HSPs. Its efficacy will now have to be tested on primary cells derived from people with CF who carry other mutations in order to assess its therapeutic potential. 

The study of the second compound is still ongoing, and it will be necessary to wait for the results of the experiments with primary cells.