This summer, I indulged and watched a bunch of rom-coms. The most recent of them was Five Feet Apart, which features two teenagers living with cystic fibrosis (CF). The movie’s depiction of CF sparked my interest, and thus this article was born.
Affecting roughly 35,000 people in the United States, CF is an inherited, progressive disease that affects mucus production in the body. Mucus should be thin and free flowing, as it lubricates and protects the lining of the airways, reproductive system, digestive system, and other tissues. As mucus is present throughout the body, CF impacts all organs, although it primarily causes issues in the lungs and pancreas.
CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, causing the CFTR protein to be either missing or defective. The CFTR protein acts as a channel across cell membranes, allowing for the movement of chloride ions (from salt). Chloride ions are negatively charged, attracting the positive ends of polar water molecules. This attraction allows water to move to the cell surface, creating a thin mucus. However, when the CFTR protein is dysfunctional, chloride cannot move and attract water, causing mucus to become thick and sticky. Thick mucus is unable to flow and move throughout the body, and builds up and clogs tubes and ducts.
Built-up mucus has many negative effects on the body. In the lungs, the mucus clogs up the airways and traps many germs and bacteria. This can cause infection, inflammation, respiratory failure, and a number of other complications. As a result, people with CF must do their best to avoid illness, because even a simple cold can cause devastating consequences. This means CF patients must stay up to date with immunizations like the flu vaccine. Additionally, CF patients must avoid close contact with people with respiratory illnesses, which can be achieved by wearing a mask and keeping a safe distance away. One unique thing about CF, however, is that patients must avoid others with CF. As portrayed in the film Five Feet Apart, CF patients must never interact in a face-to-face situation, as each CF patient can carry infections and pathogens that will solely affect other CF patients. These pathogens are often very resilient and don’t respond to antibiotics, thus the name “super bugs” emerged to describe specific pathogens that are passed between CF patients that cannot be eliminated. In the pancreas, mucus buildup prevents the release of digestive enzymes that help the body get its nutrients, resulting in malnutrition and poor growth.
Like many other genetic diseases, CF has no cure. However, starting in 1989 with the discovery of the CFTR gene, our understanding about CFTR and CF has grown, and the path to discovering a cure has become more plausible.
First, researchers were able to classify mutations of the CFTR gene in CF patients into different groups. In some cases, the mutant CFTR gene encodes a protein that is folded incorrectly, thus making it unable to reach the cell’s surface or function properly. In other cases, the mutations stop the CFTR protein from being created at all.
This research on classifying different CFTR mutations has led to the development of certain treatments, such as CFTR modulators. CFTR modulators can improve the function of a defective CFTR protein in CF patients. The first Food and Drug Administration (FDA) approved drug of this type is called ivacaftor and is able to restore around fifty percent of CFTR protein function.
Following the development of ivacaftor, several additional modulator drugs have been developed and approved by the FDA. Excitingly, a combination of modulator drugs including ivacaftor, lumacaftor and trikafta can further restore the functions of defective CFTR proteins. This significantly improves the quality of life for CF patients and allows them to spend more time with family and friends, as they gain lung function, have fewer body aches, and have an increased appetite without nausea. Additional studies on CFTR modulator drugs are currently being conducted to see if longer intervention times can lead to better outcomes. Scientists believe that if CF patients take CFTR modulators from a young age, they can avoid severe multi-organ problems and live a regular life with a normal lifespan.
However, around ten percent of CF patients cannot be helped by therapies using CFTR modulator drugs because these patients do not make the CFTR protein at all. The University of Illinois Urbana-Champaign and the Carver College of Medicine at the University of Iowa are working together to develop alternative therapies. They have recently developed a new drug called CM001, which is intended to stand in as a protein channel in CF patients where the CFTR protein is missing or dysfunctional. In essence, this drug is an inhalable molecular prosthetic. Clinical trials are currently open to CF patients. If the drug is successful, all CF patients, no matter what type of CFTR mutations they have, would be able to get some type of relief and an increase in lung performance.
The development of these different treatment options have drastically helped CF patients, and will continue to do so in the coming years. As technology advances, it is clear that finding a cure for CF is close, bringing hope to thousands of people who are affected by this devastating disease.
Human lungs. Australian Physiotherapy Association