By Marisa Ruwe and Taylor Thomas, second year genetic counseling students
What is Cystic Fibrosis?
Each year, Cystic Fibrosis Awareness Month is recognized throughout May. Cystic fibrosis (CF) is a genetic condition estimated to impact over 100,000 people of all racial and ethnic backgrounds worldwide. The genetic changes that cause CF result in the production and buildup of thick, sticky mucus throughout the body. While most tend to think of CF as a lung disease, this condition can also have a significant impact on the digestive system (particularly the pancreas) and other organs. Difficulty breathing, frequent infections, malnutrition, and male infertility are some of the symptoms experienced by those with CF.
Cystic fibrosis is caused by changes in both copies of a person’s CFTR (cystic fibrosis transmembrane conductance regulator) gene that result in both copies of the gene not functioning properly. The CFTR gene provides instructions for the body to produce CFTR proteins, which are like tunnels with gates located on the surfaces of certain cells that control the concentrations of salt and water present in places such as the surface of the lungs. Some changes to the CFTR gene reduce the number of CFTR proteins produced, while others instead reduce the function or alter the structure of the CFTR proteins. These disease-causing changes in CFTR ultimately lead to an imbalance of salt and water concentrations on cell surfaces, which then leads to the production of the thick, sticky mucus seen in CF.
The Gold Standard of Cystic Fibrosis Diagnosis
Over 75 years ago, an intense New York City heat wave led to an important discovery that would have a major impact on our understanding of cystic fibrosis and our ability to diagnose it. During this heat wave in 1948, Dr. Paul di Sant’Agnese, a physician at Columbia-Presbyterian Medical Center, noticed that the CF patients under his care left white, salty handprints on their water glasses. This keen observation led di Sant’Agnese to research the sweat contents of those with CF, leading to the discovery that their sweat contained significantly higher levels of salt (sodium, chloride, and potassium) than those without CF. Subsequent research performed based on this discovery led to the development of the accurate and non-invasive “sweat test” to measure chloride content in patients’ sweat that remains the gold standard for diagnosing patients with CF to this day5.
A Changing Prognosis
Although the gold standard for diagnosis of cystic fibrosis has remained steadfast for decades, the treatments available for CF patients have changed significantly during this time. Historically, the treatment of CF was limited to symptom management, with patients being given bleak prognoses and having substantially shortened lifespans. However, the recent development of CFTR modulating medications has revolutionized CF care and significantly transformed the outlook for many CF patients.
Rather than treating the symptoms of cystic fibrosis, CFTR modulating medications target the underlying cause of CF – the CFTR proteins themselves. This is accomplished by the administration of medications that improve the structure and/or function of CFTR proteins in the body. For many CF patients, treatment with modulating medications have resulted in improvements to lung function, reduced hospitalizations, improved quality of life, and an increased life expectancy.
Unfortunately, because several different types and combinations of genetic changes to the CFTR gene can cause cystic fibrosis, not all CF patients will respond in the same way to CFTR modulating therapies. Approximately 10% of CF patients have genetic changes that will not respond to treatment with CFTRmodulators2. Hundreds of disease-causing changes in CFTRhave been discovered so far, and there is still significant room for improving our understanding of rare CFTR genetic changes and the development of new treatments to ensure that eventually all CF patients can receive the treatment they need to thrive.
Future Therapies
In addition to today’s available therapies, gene editing technologies like CRISPR offer exciting prospects for correcting the genetic changes responsible for CF at the cellular level1,4. While still in the early stages of development, these cutting-edge approaches hold potential for providing long-term solutions to this condition. Living with CF presents a myriad of challenges, from managing infections to navigating complex treatment regimens3. Efforts to overcome hurdles such as immune responses to viral delivery and penetration through thick mucus layers are underway, fueled by rapid developments in gene engineering technology3. Although FDA-approved CF gene therapies are yet to materialize, ongoing research holds promise for more efficient and effective treatments soon.
Ongoing Clinical Trials
Clinical trials serve as crucial avenues for evaluating novel therapies and expanding treatment options for CF patients. From CFTR modulators to gene editing techniques, a myriad of trials is underway worldwide4. By participating in clinical research, patients not only gain access to potentially life-changing interventions but also contribute to the advancement of scientific knowledge.
Call to Action
Despite advancements, challenges persist in CF care. Drug costs remain high, limiting access for many patients2. As we envision the future of CF treatment, it is essential to address these challenges and advocate for accessible, patient-centered care. Research efforts must continue to focus on developing alternative therapies for individuals with CFTR mutations that are unresponsive to current modulator therapy.
Raising Awareness of the CF Community
Advocacy and community involvement in supporting research initiatives and improving access to care for individuals living with CF is vital. By amplifying patient voices, advocating for research funding, and fostering collaboration, we can drive progress towards better treatments and, ultimately, a cure for cystic fibrosis. The collective efforts of researchers, healthcare professionals, patients, and advocates offer hope for a brighter future for those affected by CF. Together, we can continue to support the CF community.
Join the Omaha community at the Cystic Fibrosis Foundation’s 2024 Great Strides Walk on June 1st in Turner Park Omaha, NE! Great Strides is a community walk to celebrate the great strides made in CF treatment. Great Strides walkers can participate in person or virtually. All participants can fundraise with tools in the Fight CF mobile app or with Facebook Fundraising. The Cystic Fibrosis Foundation is a national organization dedicated to ongoing research for CF treatments, with the hope of eventually curing this disease. To learn more, visit the Cystic Fibrosis Foundation website.
References
- Allen, L., Allen, L., Carr, S.B. et al. Future therapies for cystic fibrosis. Nat Commun 14, 693 (2023). https://doi.org/10.1038/s41467-023-36244-2
- Fajac, I., & Sermet, I. (2021). Therapeutic Approaches for Patients with Cystic Fibrosis Not Eligible for Current CFTR Modulators. Cells, 10(10), 2793. https://doi.org/10.3390/cells10102793
- Home Page: Journal of cystic fibrosis. Standards for the Care of People with Cystic Fibrosis; Establishing and Maintaining Health. (2023, December 21). https://www.cysticfibrosisjournal.com/
- Lomunova, M. A., & Gershovich, P. M. (2023). Gene Therapy for Cystic Fibrosis: Recent Advances and Future Prospects. Acta naturae, 15(2), 20–31. https://doi.org/10.32607/actanaturae.11708
- McAlindon, D. (2022). A legacy of changing medicine: Cystic fibrosis. Retrieved from https://www.cuimc.columbia.edu/news/legacy-changing-medicine-cystic-fibrosis
- Rowbotham, N. J. et al. The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers. Thorax 73, 388–390 (2018).