July 16 ~ Written By Amna Farhan

Cystic fibrosis (CF) is a fatal genetic disease that is inherited in an autosomal recessive pattern, meaning that individuals with mutations in both copies of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene will be affected by the disease. The CFTR gene encodes for the ion protein channel that regulates the transport of chloride and water through mucus producing cells. When this transport is disrupted, thick and sticky mucus starts obstructing pathways. But why is there currently no cure for cystic fibrosis?

Firstly, more than 50% of adults with CF in the US are infected with Pseudomonas aeruginosa, of which approximately one-third is resistant to more than one antibiotic. The infection’s multidrug-resistance is explained by its ability to adapt to its environment, after which it develops resistance to the antibiotic that is being used to treat it. This is not the only reason, there are also multiple microorganisms present in the lungs that affect the infection’s ability to resist antibiotics.

Secondly, modelling the lungs of someone with cystic fibrosis effectively is also very crucial. This needs to be done in order to see and better understand what is actually going on inside the lungs of a CF patient. This can’t be done using scans because when a patient coughs up a sample, it could be from any part of the lung . Clinicians don’t have a way of knowing what part of the lungs the sample came from. Not knowing where the actual problem lies makes finding a cure even harder.

The CFTR modulator drugs are regarded as a breakthrough in the treatment of cystic fibrosis. In CF patients the transport of chloride and water through mucus producing cells is disrupted causing thick and sticky mucus to obstruct pathways so these CFTR modulator drugs create channels for the chloride and water to pass and prevent 2 mucus from obstructing pathways. There are four CFTR modulators for people with certain CFTR mutations: Trikafta® (elexacaftor/tezacaftor/ivacaftor) which has been approved for people age 12 years and older and has also been approved by the FDA for children between the age of 2 to 5 with certain CF mutations, Symdeko® (tezacaftor/ivacaftor) which has been approved for people age 6 years and older, Orkambi® (lumacaftor/ivacaftor) which has been approved for people who are age 2 years and older. and Kalydeco® (ivacaftor) which has been approved for people who are 6 months and older. However, there are more than 2,500 mutations of the CFTR gene. These modulator drugs can’t be used for every single mutation of the CFTR gene. For example, Trikafta is used for the most common CF mutation that only 90% of CF patients have. What about the remaining 10%?

CFTR modulators also include CFTR amplifiers these increase the number of CFTR proteins that are present on the cell surface; this results in increased flow of chloride ions across the cell membrane (amplifiers are just being tested right now and are currently not available commercially).

However, researchers aren’t sure if modulator drugs will be a permanent solution for patients. Although there are many effective drugs and treatments for Cystic Fibrosis it still remains without a fully effective cure.

References

“Cystic Fibrosis Breakthrough.” University of Kansas Medical Center, https://www.kumc.edu/school-of-medicine/about/ku-medicine-magazine/winter-202 1/cystic-fibrosis-breakthrough.html.“Our History.” Cystic Fibrosis Foundation. https://www.cff.org/about-us/our-history.

“Cystic fibrosis - Diagnosis and treatment.” Mayo Clinic, 23 November 2021, https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/diagnosis-treatment/ drc-20353706.

“The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics.” NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684810/.

Claire, Jarvis and Gwyn, William. “Why is cystic fibrosis so hard to treat?” Chemistry World, 10 August 2020, https://www.chemistryworld.com/features/why-is-cystic-fibrosis-so-hard-to-treat/40 12206.article.

“Types of CFTR Mutations.” Cystic Fibrosis News Today, 5 April 2023, https://cysticfibrosisnewstoday.com/types-of-cftr-mutations/.