Posted by The top image is a cell with a mutation causing CF, the bottom image is that same cell after treatment using Trikafta.
Trikafta as a new treatment for Cystic Fibrosis
The top image is a cell with a mutation causing CF, the bottom image is that same cell after treatment using Trikafta.
While Cystic Fibrosis affects more than just the respiratory system, I will be using it to analyze the effects of disease on structure and function of the respiratory system and then how a new treatment for the disease corrects the differences in structure and function. First it’s important to establish what exactly Cystic Fibrosis (CF) is. The disease is a genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; this mutation causes the corresponding CFTR proteins to be dysfunctional. The CFTR protein functions by moving chloride across the cell membrane in order to attract water and produce mucus of the desired consistency. When this protein is dysfunctional it may not be produced enough, be produced improperly, or not make it to the cell membrane. In the body this affects all mucus producing organs primarily the lungs, pancreas, and liver. In the lungs and sinuses the mucus can clog airways with thick mucus which traps germs and increases the risk of infection. In the liver and pancreas the buildup of mucus makes it difficult to release the necessary digestive enzymes and can clog ducts leading to malnutrition. In men CF also affects their ability to have children. An interesting way to tell if someone has CF is the salt content of their sweat, a child with CF tastes salty when you kiss them. Because of this the folklore was that if a child tastes salty from a kiss on the brow they are cursed and soon to die. Until relatively recently CF and its cause has been a mystery.
With modern medicine there has been a lot of research on CF both to understand and cure the disease, one of those most recent breakthroughs is the development of the drug Trikafta. Trikafta is a combination of three different drugs which all aid in getting CFTR proteins to be made properly and brought to the cell membrane. The first two elexacaftor and Tezacaftor work together to get more CFTR proteins to reach the surface of the cell. And Ivacaftor, the last of the trio, helps the proteins stay open longer, allowing more ions to pass through. Even though this is still a relatively new drug it has been absolutely game changing in the CF community. Patients who are taking the drug have seen increase in lung function, weight gain, and all around health. The FDA is currently going through trials to test the drug for younger patients in order to potentially avoid long term damage seen in older CF patients. With the use of this drug various other treatments that were previously necessary have been considered to be phased out of treatment plans. That’s not to say there aren’t risks, drug injury to the liver is a relatively common side effect which usually requires stopping the drug to allow for further testing. And the effects of CF often worsen after stopping treatment with Trikafta in comparison with before taking the drug. Clearly further research needs to be done to lessen side effects while maintaining the effectiveness, but overall Trikafta has been an amazing breakthrough in treatment for CF.
Jessica Gimarc’s STEAM project is on Cystic Fibrosis, its effects on the body and the breakthrough drug Trikafta. While Cystic Fibrosis is larger in scope than the respiratory system, Jessica’s STEAM project limits itself to the respiratory system to better understand how the disease acts and how Trikafta corrects the abnormalities. As stated, Cystic Fibrosis is a genetic disorder due to mutation of the cystic fibroids transmembrane conductance regulator (CFTR) gene. The mutation of one cause corresponding proteins to also mutate. The CFTR protein’s function is to move chloride across cell membranes in order to increase osmolarity concentrations and draw water to one side of the membrane. This in turn varies mucus thickness to desired consistency. When dysregulation occurs, improper levels of mucus may be produced varying from too little to too much. This causes cascade effects in all mucus secreting organs, notably airways. Clinical indicators of CF may include higher sodium concentrations in sweat. Trikafta is a polypharmacy therapy designed to bring protein production of CFTR back into a normal state and corrected proteins into the affected cell membranes. Elexacaftor and Tezacaftor act in tandem to increase transport of CFTR proteins to cell surfaces. Ivacaftor, the third drug, works by maintaining the CFTR protein’s ion channels for longer to allow more transport of sodium and chloride ions. This therapy, while still new to the market, has been shown to increase lung function, better weight maintenance, and increases in overall heath and quality of life. FDA review is underway to determine safety for adolescents and children with CF. Known side effects include drug toxicity to the liver requiring cessation of therapy and may lead to worsened outcomes when stopped. This breakthrough drug still requires further testing and refinement; however, is a much-needed step for CF treatment.