A possible cure for Cystic Fibrosis?

Author: Tashi Mosali, Y11

Cystic fibrosis is a rare genetic disease that can be caused if the gene that contains a protein called cystic fibrosis transmembrane regulator (CFTR) is inherited from both parents as it is a recessive disease. As a result of the mutations that occur in this gene, a patient with CF could either produce an abnormal version of this protein or no protein at all making them dysfunctional. It can severely affect the cells in our body creating a negative impact on our body. When the protein is defective, it is unable to move chloride to the cell surface and as a result cannot attract water to the cell surface which leads to the mucus present in multiple organs to become thick and sticky. When the mucus obstructs the airway there is a high possibility of complications such as respiratory failure, inflammation and infections due to the build-up of bacteria.

Cystic Fibrosis is a progressive disease which means the patient’s condition can worsen and become a growing threat. Therefore it requires daily care that includes a combination of therapies in order to help control the symptoms and improve life quality. This can include: airway clearance to loosen and get rid of the thick mucus that is built up in the lungs by coughing or huffing, pancreatic enzyme supplements which are taken with every meal in order to maximise the absorption of essential nutrients, medication in the form of mist or aerosol that are inhaled through a nebulizer in order to carry antibiotics into the blood which will help the immune system fight lung infections and many more.

There had been no development of a treatment for CF until 2019 when Trikafta was introduced by Vertex Pharmaceuticals. A triple combination therapy than consists of three modulators(substance that alters the activity of a molecule): elexacaftor, tezacaftor and ivacaftor. The treatment is said to work as the correctors- tezacaftor and elexacaftor- bind to the defective CFTR proteins and correct the way it folds which allows more protein to be transported to the cell membrane rather than being degraded, while the potentiator- ivacaftor- improves the flow of chloride molecules. On October 21st 2019, Trikafta was approved by the U.S Food and Drug Administration (FDA) for all CF patients over the age of 12 with at least one specific mutation of the CFTR gene- F508del- which has been estimated to be present in approximately 90% of the cystic fibrosis patient population. This judgement was based on two clinical trials that took place which resulted in a 3% increased lung function, a better BMI, reduced levels of salt in the sweat produced as well as alleviated respiratory symptoms. On the other hand, it seems to be very expensive which some patients find concerning and includes side effects as most medications do such as headaches, diarrhoea, abdominal pain, etc.

Despite the positive results Trikafta has provided for those that have taken part in the clinical trials, there are still more trials that are set to take place in order to enhance a further understanding of the toxicity and dosage of the drug as well as to develop a version of the treatment that benefits patients of all ages and with a variety of conditions hopefully leading to a cure for cystic fibrosis in the near future.