A New Therapeutic Treatment for Cystic Fibrosis

Since the discovery of cystic fibrosis (CF) in 1938, there have been significant increases in life expectancy for those with CF.

Treatments such as antibiotics and physical therapy are responsible for the increased life expectancy into a person’s 30s.⁴ 

However, these treatments still have limits as they do not directly target the problem behind CF – a genetic mutation. Nevertheless, a new study shows that with gene therapy, people with cystic fibrosis can alleviate symptoms while improving their quality of life. 

What is cystic fibrosis?

Cystic fibrosis is commonly linked to a genetic mutation relating to a protein called cystic fibrosis transmembrane conductance regulator (CFTR).¹ The gene mutation is often the result of faulty instructions.

This mutation causes low production of the protein or its absence altogether. 

This protein is essential as it balances the water movement in tissues and produces mucus, sweat, saliva, tears, and digestive enzymes.² Low levels of this protein cause the irregular function of the lungs, pancreas, liver, intestine, and reproductive organs¹. 

Patients with CF often produce an excess amount of mucus with less control over the balance of water in tissues. This mucus traps bacteria, causing infection and inflammation in the airways.³ 

A promising treatment for cystic fibrosis

Results of a recent clinical trial study showed that the use of antisense oligonucleotides (ASO) – molecules that control protein levels in cells, could create functioning versions of CFTR.⁵

The study focused on gene therapy using ASOs to make instructions in cells to create imperfect versions of CFTR. 

These imperfect versions of CFTR were able to improve the function of lung cells. These results are promising in advancing treatments for those with cystic fibrosis. 

Scientists are hopeful that through the use of ASO, there may be a way to have tailored therapies unique to an individual, paving the road to more personalized medicines. 

References 

1. Naehrig, S., Chao, C.-M., & Naehrlich, L. (2017). Cystic fibrosis. Deutsches Ärzteblatt International. https://doi.org/10.3238/arztebl.2017.0564 
2. Liou, T. G. (2019). The clinical biology of cystic fibrosis transmembrane regulator protein. Chest, 155(3), 605–616. https://doi.org/10.1016/j.chest.2018.10.006 
3. Bell, S. C., Mall, M. A., Gutierrez, H., Macek, M., Madge, S., Davies, J. C., Burgel, P.-R., Tullis, E., Castaños, C., Castellani, C., Byrnes, C. A., Cathcart, F., Chotirmall, S. H., Cosgriff, R., Eichler, I., Fajac, I., Goss, C. H., Drevinek, P., Farrell, P. M., … Ratjen, F. (2020). The future of cystic fibrosis care: A global perspective. The Lancet Respiratory Medicine, 8(1), 65–124. https://doi.org/10.1016/s2213-2600(19)30337-6 
4. Shteinberg, M., Haq, I. J., Polineni, D., & Davies, J. C. (2021). Cystic fibrosis. The Lancet, 397(10290), 2195–2211. https://doi.org/10.1016/s0140-6736(20)32542-3 
5. Kim, Y.J., Nomakuchi, T., Papaleonidopoulou, F. et al. Gene-specific nonsense-mediated mRNA decay targeting for cystic fibrosis therapy. Nat Commun 13, 2978 (2022). https://doi.org/10.1038/s41467-022-30668-y