I was asked a question about my thoughts on CFTR modulators versus gene therapy, and thought I would add it as a post here:

CFTR Modulators:

Currently about 95% of the population in Australia have F508del or a gating/residual function mutation, and will hopefully benefit from the CFTR modulator meds by Vertex, N30 and other companies (such as Kalydeco, VX809, VX661, N6022 and N91115). Medications like Ataluren may help some of the remaining 5%, however it appears that a reasonable amount of future research is needed in this area. Recently a study investigating VX809 with other class 2 mutations found that several rare mutations were helped in vitro by VX809, so it is possible some of these people in this 5% may have some benefit from these medications. I would like to see more in vitro study data, especially with splicing mutations, however the best way to find out if someone in this 5% can be helped is to trial a combination of the available meds to see if they help (hopefully this will be an option in the future). The goal is personalised medications, where a specific combination and possibly even a specific dose are given to each person, based on their genes and absorption/metabolism.

Gene Therapy

I have been following the work with the gene therapy in the UK and in Australia. Whilst it appears this will take longer than the CFTR modulator approach in terms of initial access to a treatment, I hope that the gene therapy approach will get all of us closer to the 90-100% of normal CFTR function (G551D with Kalydeco is at 50% of normal function). There have been some people with G551D who have had a smaller response compared to others in terms of FEV1/sweat chloride/symptoms, so gene therapy may further help the people who do not have a large improvement with the CFTR modulators. It is also less frequent than twice a day (I think the UK gene therapy trial is a med once a month), and won’t rely on absorption with fat. So it appears there are less variables that influence how well it works, however I wonder if there are other variables that influence the gene transfer in the lungs? Such as immune response and other variables (that we may not be aware of). The main downside to gene therapy is that it currently only helps the lungs, which makes me wonder if gene therapy will be used alone in the future, or in conjunction with CFTR modulators?


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1. Class 1 Nonsense Mutations, 1. Class 2 Mutations & F508del, 1. Class 3 Gating Mutations & G551D, 1. Residual Function Mutations & R117H, 2. Gene Therapy, 3. N30 - N6022 & N91115, 3. PTC - Ataluren, 3. Vertex - Kalydeco, 3. Vertex - Second Generation Correctors, 3. Vertex - VX809 & VX661