Cystic fibrosis is a genetic disease that affects mucus and sweat glands. It causes a build-up of mucus that leads to problems with the lungs, pancreas, liver, intestines, and other systems of the body. People with cystic fibrosis experience frequent and severe health complications and early mortality. However, research on the disease has improved current treatments, increasing life expectancy to about 37 years of age in the U.S.
Recent advances in the understanding about and treatment of cystic fibrosis include breakthroughs in the genetics of the disease, the development of new drugs, and studies of the root causes of cystic fibrosis.
In 2000, researchers mapped the entire genetic structure of Pseudomonas aeruginosa, the bacteria that is the most common cause of lung infections in cystic fibrosis. That work paved the way for the development of better antibiotic therapies for lung infections. A new antibiotic delivered by inhalation has been developed for people with cystic fibrosis who have recurrent infections that are resistant to standard antibiotics.
In 2003, scientists at Structural GenomiX Inc. solved the three-dimensional structure of part of the CFTR protein, which helped drug researchers develop new approaches to fighting the disease. CFTR (cystic fibrosis transmembrane conductance regulator) is a type of protein known as an ion channel. It transports salt molecules in and out of cells. Mutations in the CFTR gene can cause the CFTR protein to malfunction, resulting in cystic fibrosis.
A new drug targeting CFTR was approved in 2012. In clinical trials, the drug improved symptoms of cystic fibrosis in people with a specific type of mutation, called G551D. That success led to subsequent approval of treatment for dozens of additional mutations, including F508del, which affects about a third of cystic fibrosis patients in the U.S.
In the Pipeline
The latest new therapies for cystic fibrosis focus on restoring the function of the CFTR gene. However, the research pipeline includes other types of therapies including mucociliary clearance, anti-inflammatory, antimicrobial, and nutrition.
Scientists are gaining a better understanding of the root causes of cystic fibrosis. For example, the most common mutation leading to cystic fibrosis, F508del, causes the CFTR protein to misfold, resulting in a distorted conformation and malfunction of the protein. A new study by scientists at the Scripps Research Institute showed that the mis-folded version of CFTR interacted with a network of different proteins compared to the functional version. When they used gene silencing technology to knock down those dysfunctional interactions, the mutated CFTR protein returned to normal function. This research could lead to therapies that restore full normal function to the lungs and other organs affected by the F508del mutation in cystic fibrosis.
Another recent discovery from Queen’s University Belfast showed that fat-soluble vitamins can improve the effectiveness of antibiotics used in the treatment of lung infections in cystic fibrosis. This is due to the physiologic function of lipocalins, which capture antibiotics, preventing them from entering and killing bacteria. Lipocalins contribute to antibiotic resistance. But lipocalins have a greater affinity for fat-soluble vitamins like vitamin E than they do for antibiotics, so higher doses of fat-soluble vitamins may increase the effectiveness of antibiotics in those infections.
Cystic fibrosis has many fruitful areas of research offering hope to patients who suffer from the disease and their families. These research efforts could lead to new treatments for cystic fibrosis and its complications, or even a complete cure for the disease.
Reviewed by Liji Thomas, MD
- Cystic Fibrosis, https://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=36
- About Cystic Fibrosis, https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/
- Scripps Research Institute, Scientists Find Protein ‘Talks’ to Wrong Partners in Cystic Fibrosis, http://www.scripps.edu/newsandviews/e_20151207/yates.html
- Queens Research Discovers Vitamins Could Help Treat Cystic Fibrosis, http://www.qub.ac.uk/Connect/News/Allnews/QueensResearchdiscoversvitaminscouldhelptreatCysticFibrosis.html
- Johns Hopkins Cystic Fibrosis Center, http://www.hopkinscf.org/research/