Cystic Fibrosis Research

• Medicines that address underlying causes: NHLBI’s lung program supported decades of research to understand the structure and function of a lung protein that is genetically changed by cystic fibrosis. This foundational work led to the industry discovery of ivacaftor, the first drug to treat the underlying cause of cystic fibrosis, which the U.S. Food and Drug Administration (FDA) approved in 2012.
• Effective combination therapies: NHLBI-supported clinical trials led to the approval of a triple combination of CFTR modulator medicines that improves lung function in about 90% of people who have cystic fibrosis. However, further studies have shown that people of color are less likely than white people to have mutations that are eligible for treatment with current CFTR modulators. Researchers supported in part by the NHLBI are investigating these disparities. The Institute is also funding projects to develop treatments that will work for people who have less common CFTR mutations.
• Remote monitoring of lung health: As COVID-19 made in-person healthcare visits more challenging, an NHLBI-funded study developed an at-home diagnostic tool for measuring how well the lungs work. The FDA-cleared system uses a handheld breathing device and a mobile app called Breathe Easy. Patients blow into the device and communicate directly with their healthcare provider, who can monitor how well their lungs are working and adjust medicines as needed. Between April 2020 and May 2021, the Cystic Fibrosis Foundation distributed nearly 20,000 of the devices to people with cystic fibrosis in the United States. A study showed results were reliable 81% of the time for a sample of 48 patients who used the portable device with the app.

Our Division of Lung Diseases and its Airway Biology and Disease Branch oversee much of the research on cystic fibrosis that we fund.

• Biomarkers of declining lung function: The NHLBI Catalyze Program is supporting the development of a biomarker-based platform that predicts lung function decline in patients with cystic fibrosis and a web-based application to inform physicians when a patient may require therapeutic interventions.
• More options for disease modulators: Investigators are studying CFTR protein folding and the use of modulators for patients with rare variant mutations not typically eligible for cystic fibrosis modulator therapy.
• Monitoring methods with fewer side effects: Researchers are combining noninvasive, radiation-free imaging and proteomic biomarkers to diagnose and monitor lung disease progression in kids with cystic fibrosis.

Current research on cystic fibrosis treatments

• New treatment strategies: Although treatments improve lung function for many living with cystic fibrosis, some people have CFTR mutations that do not respond to available CFTR modulators. Even those whose disease responds to CFTR modulators still have trouble clearing bacteria out of their lungs. We are supporting a project, Novel Strategies to Clear Bacteria from the CF Lung, that aims to develop an inhaled medicine to shift the lung’s immune balance to help clear bacteria from lungs of people with cystic fibrosis.
• New treatment mechanisms: NHLBI-funded studies are testing whether a medicine to correct acid problems in the blood can also help reduce acid levels in the airways, which can then prevent or slow the development of cystic fibrosis.
• Better medicines to fight mucus: Researchers are developing new medicines to help clear and target the thick mucus found in cystic fibrosis lungs and improve how well the lungs work. This can also help prevent inflammation and infection.
• Antibiotic alternatives: Investigators are studying the thiocyanate (SCN−) analog selenocyanate (SeCN−) as an alternative therapeutic for the treatment of cystic fibrosis lung pathogens that are difficult to treat with current antibiotics.

NHLBI News

Watch videos of a 2022 workshop that brought together experts from the NHLBI and other parts of NIH, as well as the Cystic Fibrosis Foundation, to identify future research needs for treating cystic fibrosis.

Current research on gene editing and cystic fibrosis

The NHLBI is supporting research on new genetic therapies to treat cystic fibrosis. For example, researchers are studying state-of-the-art gene delivery tools and technologies that may be better at delivering a corrected gene to lung cells. Researchers are also working on better methods to improve genetic therapies in the laboratory before moving to clinical trials.

Through the NIH Common Fund Somatic Cell Genome Editing (SCGE) Program, the NHLBI supports studies that explore new genetic therapy approaches to repair the cystic fibrosis gene, among others.

• Gene editing for lung disease: Studies using CRISPR gene editing tools will correct genes in the cells that line the airways. Using these tools could lead to new treatments for genetic and acquired lung disease.
• Gene editing for cystic fibrosis: A research program is developing combinatorial nonviral and viral CRISPR delivery for lung diseases. These studies focus on efficiently targeting gene editing tools to diseased lung cells in people who have cystic fibrosis.

To identify research barriers and challenges to using gene editing as a means to cure cystic fibrosis, the NHLBI participated in a joint workshop with the Cystic Fibrosis Foundation in 2018. The Institute also participated in a 2020 virtual workshop to discuss challenges and opportunities that could be addressed in a potential second phase of the SCGE program.

The NHLBI funds other studies of gene editing for cystic fibrosis as well.

• Molecular targets to treat cystic fibrosis: The NHLBI supports research for new molecular therapies, including gene editing. Molecular therapies have helped restore the CFTR protein function for some but not all people with cystic fibrosis. New research uses airway cells and animal models to look for more ways to prevent and treat this condition.
• How nanoparticles may improve treatment effectiveness: To improve the delivery of gene editing tools and other therapeutics, researchers are developing more effective virus-inspired nanoparticles to penetrate mucus barriers in diseases with thick mucus like cystic fibrosis. 

Find more NHLBI-funded studies on gene editing and cystic fibrosis at NIH RePORTER.

NHLBI NEWS

Read more about NHLBI-supported research on gene editing, which involves making changes to a specific DNA sequence to correct the mutation in the cystic fibrosis gene: A cystic fibrosis cure for all? Gene editing shows promise.

Current research on understanding the causes of cystic fibrosis

• New treatment and prevention: NHLBI-supported scientists are carrying out Multi-Scale Investigations of Respiratory Mucus/Mucin Structure and Function in Health and Disease designed to build a solid foundation of knowledge about mucus, how it forms, and how it works to protect the body from infections. The resulting knowledge could lead to new ways to treat and prevent lung problems that result from the thick, sticky mucus caused by CFTR mutations.
• Origins of disease: Scientists are using a cystic fibrosis animal model to study the origins of cystic fibrosis airway disease. Researchers hope this will help speed up the development of new treatments for early lung disease.
• High-resolution imaging to better understand lung disease mechanisms: Another NHLBI-funded study uses an imaging method called optical coherence tomography (OCT) to take high-resolution images of the lungs and the nose. OCT can help researchers better understand how mucus is cleared and how cystic fibrosis affects this process.

Find more NHLBI-funded studies on the causes of cystic fibrosis at NIH RePORTER.

NHLBI IN THE PRESS

Learn more about how cystic fibrosis changes the airways’ cellular makeup: Molecular analysis identifies differences between healthy lung and lungs of people who have cystic fibrosis.

The Division of Intramural Research, which includes investigators from the Pulmonary Branch, is actively engaged in the study of cystic fibrosis.

• The Trans-Omics for Precision Medicine (TOPMed) program includes participants who have cystic fibrosis, which may help researchers understand how genes affect people and how individuals respond to treatment.
• The NHLBI-funded LungMAP research centers are creating molecular maps of the lungs to better understand rare lung diseases in children, including cystic fibrosis.