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Two Class I mutations

Hi our son has two class one mutations, 3659delC and 2183AA>G. My research has shown that these are both frame shift mutations. Are there any drugs or studies for people with two Class I mutations?
Dear questionner

Thank you for your question. As you may know Class 1 mutations cause defective protein production with premature termination of CFTR protein production. Class 1 mutations produce few or no functioning CFTR chloride channels. The 3659delC mutation has a prevalence of 0.4% and 2183AA>G has also a low prevalence. The key drugs that are being developed for Class 1 mutations include PTC124 or Ataluren. Ataluren (formerly known as PTC124) is a potential new drug for cystic fibrosis that targets these particular type of mutations also known as nonsense mutations. For patients with nonsense mutations of CF, Ataluren has the potential to address the underlying cause of the disease by allowing a full-length and functional CFTR protein to be made.
Following a number of promising early phase studies, in 2012, PTC Therapeutics released results from the Phase 3 study of Ataluren in people ages 6 and older with nonsense mutations of CF. The results showed that participants who received Ataluren over the 48 weeks of the study had a lower decline in lung function and a lower rate of pulmonary exacerbations, compared with those who took a placebo (an inactive medication or sugar pill), but this difference was not significant. Lung function was measured by FEV1 (forced expiratory volume in 1 second). A pulmonary exacerbation is a sudden worsening of symptoms of CF accompanied by a steep decline in lung function. It seems that inhaled antibiotics have a negative effect on the action of Ataluren. When analyzing only the data of patients not treated chronically by inhaled antibiotics, the decline in function and number of pulmonary exacerbations is lower for those who took the Ataluren compared with placebo. This time the difference between the two groups is greater and therefore significant. Safety results from the trial showed that Ataluren was generally well tolerated, and that the overall incidence of adverse events (unintended or unwanted events) was similar in people who took Ataluren and those on placebo.
Ataluren is an investigational drug that has not yet been approved for use by the FDA, and due to the not unambiguous data it is not known when and if all it will receive market authorization Because Ataluren is still in development, it cannot be legally purchased for use by a patient. Participants who completed the Phase 3 clinical trial of Ataluren were eligible to receive Ataluren in an ongoing extension study.
Now it has clearly to be stated, that the term “class I mutation” comprises a variety of different kinds of mutations (stop-mutations or nonsense mutations as mentioned above or e.g. frame shift mutations, as the mutations of your son mentioned in the question), all leading to a defective synthesis of the chloride channel. However, the underlying mechanisms are very different between the single types of mutations. Therefore, the results of a study for Ataluren that is effective only for nosense mutations cannot be transferred to other class I mutations, like the mentioned frame shift mutations.
Most studies that are currently underway investigate drugs or a combination of several drugs for the most common CFTR-mutation delF508. Furthermore, Kalydeco® has received market authorization for patients with at least one G551D (class III) mutation and new trials are planned to set up to test its efficacy in other class III or IV mutations.
Unfortunately, there are currently no studies underway investigating the mentioned frame shift mutations. If you want to inform yourself about the latest studies underway, please go under

I hope this information is helpful.

Best wishes

Judy Bradley
Daniela Alquen

The answer is edited by: Prof Judy Bradley