Modulators for R1162X and Q1035X

Question

Good day,

Are there any modulators available for the R1162X and Q1035X mutations? Is it to be expected that any will become available in the foreseeable future—or indeed, at any point? Is research still being conducted at all to find treatments for patients with this mutation?

Many thanks for any information.
Best regards

Answer

Dear inquirer,

First of all: it is correct that stop mutations are currently not approved for modulator therapies, as it is expected that—due to the premature "stop signal" on the mRNA (represented by the "X"—e.g., at position 1162 for R1162X, or position 1035 for Q1035X)—no functional CFTR protein will be produced.

Research is, however, ongoing into so-called "read-through" therapeutics for stop mutations. While these are not yet approved for use in patients, they would theoretically allow the cellular machinery to "read through" the stop signal, thereby producing a CFTR protein containing all its constituent building blocks (i.e., 1500 amino acids, rather than just 1162 or 1035).

R1162X is indeed a stop mutation; however, in this specific case, the production of both a CFTR transcript and a *truncated* CFTR protein is anticipated. This is not the case for many other stop mutations that are "located further upstream" within the CFTR gene—such as G542X or R553X. Therefore, it is worth inquiring at your CF care center whether modulator therapy might be a viable option in this specific instance of R1162X. The clinical severity of the disease in Italian patients carrying the R1162X mutation tends to be milder than that observed in carriers of other stop mutations (such as G542X or R553X); consequently, it is worth asking whether there are signs of residual CFTR function in your particular case (a factor that varies from patient to patient and is also age-dependent). If such residual function is present, it may be possible—in consultation with your physician—to evaluate whether modulator therapy could be effective in your specific situation.

We therefore recommend that you reach out to your dedicated CF care team. For Q1035X, it is unknown whether this stop signal leads to a complete loss of CFTR function—this cystic fibrosis mutation is too rare to provide sufficient observations.

Best regards,
Frauke Stanke

17.05.2026