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searching for the cure

the future of cf clinical trials: there's more than cftr

CFTR modulators are in vogue. I mean, I get it. They’re the first therapeutic target to directly change the underlying cause of CF. Some have found incredible success on them, others have not. And for those who have not seen incredible improvements, the research pipeline provides great hope for improved therapies in the coming years. However, we can not forget that many with CF still do not have a CFTR modulator. Some may not get one for many years. Because of this, I want to take some time to reiterate the importance of clinical trials that are not necessarily linked to treating CFTR.

  1. Another therapeutic development avenue designed to target a deregulated protein in CF is known as ENaC inhibitors. If approved, these therapies would be available to the entire CF community. ENaC is an ion channel on the surface of cells in the airway. Ion channels, like ENaC and CFTR, move ions such as sodium and chloride across cells to regulate mucus hydration. Proper ion channel function is critical to keeping mucus hydrated and freely moving. In CF, CFTR, which helps add fluid to the surface of the lung, does not work properly. However, ENaC works in the opposite way: to remove fluid from the surface of the lung. In CF, ENaC is known to be overactive, and results in more dehydrated mucus. This results in the accumulation of dehydrated mucus in the airway. This build-up of mucus is what leads to exacerbations and infections. However, airway hydration is a complicated process. Other clinical trials are also underway to address the dehydration of mucus in the CF lung. Many of these trials leverage differing therapeutic strategies to increase the amount of fluid present in the lung.

  2. Antibiotic resistance is a growing challenge in the world, with direct and unfortunate consequences for the CF community. Since people with CF can rarely eradicate infections, the bacteria acquire antibiotic resistance with chronic and periodic dosing. This makes treating infections challenging, as the bacteria stop responding to anti-infective treatments. Thus, it is essential for research to push more anti-infective therapies to market. Even with the introduction of more CFTR therapies, we still do not know how this will affect lung bacterial colonization. While new therapies are expected to make lung function better, CF patients (like all people) will eventually become sick. If antibiotic resistant bacteria are present, it will be a struggle to address the underlying infection. Because of this, we must pay special attention to clinical trials for anti-infectives.

  3. Anti-inflammatories remain another important avenue of clinical trials research in respiratory disease. CF airways tend to be more inflamed, leading to hindered mucociliary clearance and shortness of breath. The increased inflammation is also what can lead to airway remodeling, scarring and bronchiectasis. Numerous anti-inflammatory therapies are underway in clinical trial with the hope to ameliorate the inflammatory state of the CF lung. An improved inflammatory state is expected to increase lung function.

Ultimately, CF is a complicated disease with a number of symptoms arising. While CFTR is the cornerstone of many of these problems, a combination of multiple new drugs will likely lead to the best outcome for patients. These medications in clinical trial also serve as the backbone of future health for those who currently do not have a CFTR modulator. This population of people with CF represents a solid portion of our community and needs these future medications. Because of this, we must remember to advocate for their future and push the importance of clinical trials that will have a direct impact on them while they wait for a CFTR modulator.

Reid is 25 and has CF. He is a director of USACFA. His Email is:

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