Cystic fibrosis (CF) is an inherited genetic condition that impacts multiple organs throughout the body. Understanding CF’s wide-ranging effects begins by examining the specific cells involved.
The Cell Behind Cystic Fibrosis
Cystic fibrosis primarily affects epithelial cells, lining many organs such as the lungs, pancreas, digestive tract, and sweat glands. Within these cells, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is key.
The CFTR protein normally functions as a channel embedded in the cell membrane. This channel regulates chloride ion movement across the cell membrane, which is important for maintaining the balance of salt and water on cell surfaces. This balance helps keep mucus thin and flowing freely.
How the Cell Goes Wrong
Cystic fibrosis develops due to mutations in the CFTR gene located on chromosome 7. These mutations lead to the production of a faulty or entirely absent CFTR protein. A dysfunctional CFTR protein impairs normal chloride ion transport across the cell membrane. This prevents proper movement of chloride and water, leading to an imbalance of salt and water outside the cells.
Cellular Dysfunction and Its Impact
Impaired ion transport results in the characteristic thick, sticky mucus seen in CF. Without proper chloride movement, water cannot adequately hydrate the cell surface, causing the mucus to become unusually viscous. This thick, sticky mucus clogs ducts and passageways in various organs throughout the body.
In the lungs, for example, the mucus impedes the movement of tiny hair-like structures called cilia, which normally sweep mucus and trapped particles out of the airways. This blockage makes it difficult to breathe and creates an environment where bacteria can thrive, leading to frequent infections and damage to the lung tissue. In the pancreas, the thick mucus can block ducts, preventing digestive enzymes from reaching the intestines and leading to problems with nutrient absorption and digestion.
Treatments Targeting the Cell
Modern therapeutic approaches for cystic fibrosis aim to correct the underlying cellular defect. CFTR modulator therapies, such as correctors and potentiators, are key advancements. These treatments improve the function or presence of the faulty CFTR protein.
Potentiators increase the time that activated CFTR channels on the cell surface remain open, thus improving chloride flow. Correctors help the CFTR protein fold into the correct three-dimensional shape, enabling it to move to the cell surface and remain there longer. Combination therapies, which include both correctors and potentiators, can further enhance CFTR protein function, leading to improved outcomes for many individuals with CF.