Magic trio – the cure for cystic fibrosis

Cystic fibrosis is a chronic disease which until recently signalled a short lifespan with numerous complications. However, the development of new drugs has brought about significant progress in the treatment of this disease.

What is cystic fibrosis?

Cystic fibrosis is a rare hereditary disease which occurs due to a mutation of a gene on the seventh chromosome. The gene, called CFTR for short (cystic fibrosis transmembrane conductance regulator), carries the code for a protein of the same name. The CFTR protein is present in many tissues. Its function is to regulate chloride and sodium ione transport through various membranes in the body, such as those found in sweat glands, bronchi, the gastrointestinal tract and the pancreas.

Although there is a large number of possible CFTR gene mutations, the most common one is the deletion of a phenylalanine remnant in position 508, which is also denoted as ΔF508. This mutation causes less of the protein to find its way to the membrane. It also disrupts the proper opening and closing of the protein, so some of it is non-functional.

The symptoms of cystic fibrosis

Non-functional CFTR proteins can’t properly regulate the transport of chloride and sodium ions through the membrane, which leads to an accumulation of said ions and water in the cell. The change in the ion content of intracellular fluid results in a change in the consistency of gland secretions. Secretions become viscous and sticky, which causes blockages in ducts and slowly destroys glandular tissue.

Cystic fibrosis can thus manifest in any glandular tissue, but it is most noticeable in the respiratory system. Blockages in the respiratory system causes difficulties in breathing and serve as a breeding ground for bacteria. This often results in the development of chronic obstructive pulmonary disease. In the pancreas, the thick secretions cause a lack of digestive enzymes, which induces fat excretion in the stool and malnutrition. The accumulation of these secretions can lead to other complications such as liver cirrhosis, diabetes and dehydration.

New drug?

Up until recently, cystic fibrosis treatment has been focused on treating the symptoms and accompanying diseases caused by cystic fibrosis. However, in 2019, a new drug was registered. It consists of three active substances: ivacaftor, tezacaftor and elexacaftor. Elexacaftor and tezacaftor bind to CFTR proteins and lead them to the membrane, which increases their availability. Ivacaftor increases the ability of the protein to form ion channels, which improves the protein’s efficacy.

Future treatment outlooks

In clinical research, this combination of active substances has been shown to decrease chloride ion concentrations in sweat, lower the risk of developing chronic obstructive pulmonary disease, lower the number of bacterial pulmonary infections and increase quality of life for those living with cystic fibrosis. Due to its beneficial effects and minimal side effects, this trio is now considered the new golden standard in treating cystic fibrosis.