Cystic Fibrosis Research

• Medicines that address underlying causes: The NHLBI's lung program supported decades of research to understand the structure and function of the lung protein, CFTR, 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. Follow-up studies partly funded by the NHLBI have shown that ivacaftor benefits lung function and quality of life in the long term.
• Effective combination therapies: NHLBI-supported clinical trials led to the approval of a combination of three CFTR modulator medicines that improve lung function in about 90% of people with cystic fibrosis. However, 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 with less common CFTR mutations.
• Remote monitoring of lung health: As COVID-19 made in-person healthcare visits more challenging, an NHLBI-funded study led to the development of 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, through the app, 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 involving 48 patients who used the portable device with the app showed results were reliable 81% of the time.

Our Division of Lung Diseases and its Lung Development and Pediatric Diseases 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 the use of modulators for patients with rare variant mutations not eligible for current CFTR 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 children 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. An NHLBI-funded project, Novel Strategies to Clear Bacteria from the CF Lung, is testing an inhaled medicine to help restore the lung's immune balance. This could help fight bacteria and lower inflammation and lung damage.
• New treatment mechanisms: Many of the people who are not eligible for CFTR modulators have a type of mutation that stops the CFTR protein from being made. NHLBI-funded studies are testing how to suppress these mutations using engineered tRNAs — part of the cell's machinery for making proteins — to allow production of CFTR protein.
• Better medicines to fight lung bacteria and mucus: Researchers are developing new medicines to help clear the thick mucus found in cystic fibrosis lungs and improve how well the lungs work. Another NHLBI-funded project seeks to fight inflammation in the airways as a way to help clear mucus.

NHLBI News

Watch videos of a 2022 workshop that brought together experts from the NHLBI and other parts of the 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 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 with cystic fibrosis.
• Targeted Genome Editor Delivery (TARGETED) Challenge: Launched in the second phase of the SCGE program, the TARGETED Challenge aims to improve technologies for gene editing tools to speed translation of these potential therapies to the clinic.

In 2020, the NHLBI participated in a virtual workshop to discuss challenges and opportunities that could be addressed in the 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 find more ways to prevent and treat this condition.
• Improving delivery and effectiveness of gene editing: The lung is a difficult organ for gene editing and presents problems that have hindered progress in treating cystic fibrosis. Researchers are developing more effective delivery systems to get the gene editing tools to the lung and penetrate the thick mucus barrier in cystic fibrosis.

Find more NHLBI-funded studies on gene editing and cystic fibrosis at the 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 biology of cystic fibrosis

• New treatment and prevention: NHLBI-supported scientists are carrying out a project called Multi-Scale Investigations of Respiratory Mucus/Mucin Structure and Function in Health and Disease, which is 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.
• Beyond the lungs: Cystic fibrosis affects many organs and body systems. An NHLBI-funded research initiative is using many types of data and machine learning to find patterns of symptoms. The aim is to find person-centered approaches to improving the quality of life for people with cystic fibrosis.

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

The Division of Intramural Research, which includes investigators from the Critical Care Medicine and 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.