From the Guidelines
CFTR modulators are distinct from other cystic fibrosis therapies because they directly target the defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, addressing the underlying cause of the disease. They are called CFTR modulators because they work to improve the function of the CFTR protein, which is defective in people with cystic fibrosis 1. Unlike traditional CF therapies like antibiotics, mucus thinners, and bronchodilators, which manage symptoms by fighting infections, clearing mucus, or improving breathing, CFTR modulators aim to correct the root genetic problem.
Key Differences and Mechanism
CFTR modulators include medications like ivacaftor, which is a potentiator that activates defective CFTR at the cell surface 1. The primary target for this therapy is mutated CFTR, such as in cases where glycine has been replaced by aspartic acid at position 551 (G551D), interfering with the gating of the channel. These medications help the defective CFTR protein function better by either helping the protein reach the cell surface (correctors) or improving its function once there (potentiators).
Clinical Evidence and Impact
Studies have shown that CFTR modulators can significantly improve lung function, reduce pulmonary exacerbations, and improve quality of life for eligible patients 1. For example, ivacaftor has been shown to increase FEV1 by 8.7% compared to baseline and reduce the likelihood of pulmonary exacerbations by 55% 1. The specific modulator prescribed depends on a patient's genetic mutations, and these medications are taken daily. While they don't work for all CF mutations, CFTR modulators represent a significant advancement in the treatment of cystic fibrosis, offering a targeted approach to managing the disease. Traditional symptom management therapies remain important components of comprehensive CF care.
From the Research
Differences between CFTR Modulators and Other Cystic Fibrosis Therapies
- CFTR modulators are a class of small-molecule therapies that target the underlying cause of cystic fibrosis, which is the defective CFTR protein 2, 3, 4.
- Unlike traditional treatments that focus on managing symptoms, CFTR modulators aim to restore the function of the CFTR protein, improving lung function, sweat chloride levels, quality of life, and survival 2, 3.
- CFTR modulators are classified into different groups, including potentiators, correctors, stabilizers, read-through agents, and amplifiers, depending on their effects on CFTR mutations 4.
Why are they Called CFTR Modulators?
- CFTR modulators are called so because they target the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is the underlying cause of cystic fibrosis 2, 3, 4.
- The name CFTR modulator refers to the drug's ability to modify or restore the function of the CFTR protein, which is impaired in patients with cystic fibrosis 2, 3, 4.
- The development of CFTR modulators has transformed the treatment of cystic fibrosis, offering a more targeted and effective approach to managing the disease 2, 3, 4.
Types of CFTR Modulators
- Potentiators, such as ivacaftor, aim to increase the activity of the CFTR protein 2, 3.
- Correctors, such as lumacaftor and tezacaftor, aim to restore the function of the CFTR protein by correcting its folding and trafficking defects 2, 3.
- Combination therapies, such as ivacaftor/lumacaftor and ivacaftor/tezacaftor, bring together a potentiator and a corrector to target specific mutations 2, 3.
- Triple-combination CFTR modulators, such as ivacaftor/tezacaftor/elexacaftor, are now the standard of care for most CF patients, offering improved efficacy and safety 3.