What is Cystic Fibrosis?

Cystic fibrosis (CF) is an inherited genetic disorder that is characterized by the buildup of thick mucus secretions in the airways and digestive tract. This mucus makes it very difficult to breathe and digest food. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A mutation is a permanent change in the sequence of DNA that codes for a gene. Everyone has two copies of each gene (one inherited from each parent) that provide the instructions for making the proteins necessary for the body to function properly. Each of an individual’s CFTR genes needs to have a mutation for them to have CF. The parents of a child with CF often both carry a gene mutation in one of their CFTR genes, and they do not show any symptoms of the disorder. This is known as recessive inheritance.

What are the symptoms of Cystic Fibrosis?

Mucus is a normal bodily secretion used to protect the linings of the airways, digestive tract, and other bodily systems. In CF patients, this mucus is abnormally thick and can clog the systems in the body it was meant to protect. A blockage in the airway can lead to severe breathing problems, chronic coughing, inflammation, bacterial respiratory infections, and scarring (fibrosis) of the lungs. The mucus in CF patients can also damage the pancreas, an organ responsible for controlling blood sugar levels by producing a hormone known as insulin. Damage to the pancreas also interferes with its ability to produce enzymes needed to break down food into energy. As a result, CF patients may experience malnutrition, weight loss, diarrhea, greasy or oily stools, and intestinal blockages.

What causes Cystic Fibrosis?

CF develops due to mutations in the CFTR gene, which makes a transmembrane protein. A transmembrane protein is embedded in the outer boundary of a cell, known as the membrane. Its position in the cell membrane allows this protein to act as a channel linking the outside environment to the inside of the cell (like a doorway). CFTR can be found in cells that produce sweat, tears, digestive enzymes, and mucus. The channel formed by CFTR helps charged particles called ions to move in and out of cells easily. This allows cells to control the movement of water and form a mucus layer to protect the airways, digestive system, reproductive system, and other organ systems. A mutation in the CFTR gene changes the way that the protein is put together, with the most common mutation causing the channel to fall apart as soon as it is built. Without the protein helping to move ions across the cell membrane and control the flow of water, there is less water in the mucus than there should be, and a thick form of mucus is produced. Instead of providing tissues with a thin layer of protection, this sticky mucus clogs airways and forms blockages in the digestive system.

What is the treatment for Cystic Fibrosis?

CF cannot be cured, but the symptoms can be treated. Advancing treatment with triple therapy (elexacaftor/ivacaftor/tezacaftor), or a subset of these, restores the proper functions of the CFTR protein. Life-long treatment for CF can include medications to help the body absorb more nutrients from food, a high-calorie diet supplemented with vitamins, therapies to help clear mucus from their lungs, and extensive control of bacterial infections.

3D Models for CFTR