A Cure For Cystic Fibrosis?

Ever since scientists discovered the genetic cause of cystic fibrosis, patients and doctors alike have dreamt of a treatment for this life-threatening disease. This dream came true on October 31, 2019, when a three-drug combination named Trikafka was unveiled at a national conference in Tennessee, and the study behind it was published in two leading medical journals. Previously, people with cystic fibrosis didn’t even go to college because they knew they wouldn’t survive long after. With the widespread recognition of Trikafka as an effective treatment of the disease, they are now making plans for retirement.

Cystic fibrosis is a genetic disease that causes mucus and bacteria to build up in a patient’s lungs, putting them at risk for infection and making it difficult to breathe. It is caused by a specific type of gene mutation (called a point mutation) in the DNA that either adds a base pair, deletes it, or substitutes it for another base pair. The most common form of cystic fibrosis deletes a base pair in DNA, but other variations of the disease have different types of point mutations either on the same or different regions of DNA. However, what they all have in common is their position on a gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR). This protein normally transports chloride ions to the surface of a cell, attracting water to the cell as a result. The water then clears out the mucus that builds up in the airways of our lungs.

However, cystic fibrosis causes the CFTR protein to be misfolded, rendering it unable to effectively carry chloride ions. When this happens, the mucus in various organs, including the lungs, builds up and becomes thick and sticky. The mucus clogs the airways and traps germs in the surrounding tissue, leading to a high risk of infection for cystic fibrosis patients. The mucus can also lead to inflammation, respiratory failure, and other complications. Its adverse effects are not restricted to the lungs either, as mucus can also disrupt key biological processes in the pancreas and liver.

The difference between Trikafka and previous treatments for cystic fibrosis is that the former covers a wider range of patients than previous drugs did while also targeting the genetic roots of the disease. Before Trikafka, treatments to cystic fibrosis included airway clearance, which involves coughing or huffing to loosen mucus from airway walls, and inhaled medicines, which clear thin mucus from lung airways. Because cystic fibrosis is a disease with many different causes, old drug combos such as lumacaftor combined with ivacaftor had limited success since they only addressed 50 percent of the population of cystic fibrosis patients. However, Trikafka is different from all these treatments because it is effective in 90 percent of all patients, nearly the entirety of everyone afflicted with this life-threatening disease.

Trikafka works by combining three separate drugs to treat cystic fibrosis, one of which corrects the misfolded CFTR protein and the other two which activate the correctly-folded protein once it reaches the cell membrane in order to allow chloride ions to flow through. This three-drug combination was so powerful and persuasive that the Food and Drug Administration approved of it five months in advance of the agency’s deadline for the drug. Trikafka may well be compared to the invention of insulin treatments for diabetes—before a proper tool was discovered to treat this disease, patients were expected to die as early as in their teenage years. Now, with a whole new life in front of them, many patients suffering from cystic fibrosis are overjoyed at this discovery which took 30 years of advances, setbacks, and incremental improvements. “We’ve finally reached the time that an improvement is possible. To think of my lung function improving or my digestion increasing or even adding a few years to my life that I could spend with my daughter… Now that it’s available, I’m a little like, ‘Is this really happening?’” one patient stated.

Yet there’s a catch. Since this treatment only works for roughly 90 percent of cystic fibrosis patients, the remaining 10 percent still have to face their looming short life expectancy. Furthermore, Trikafka is only available for patients aged 12 and up. With these restrictions, there is a whole other side to the equation. While everyone else is celebrating, a few select patients have to wait and hope that a treatment for them is developed. “It’s really heartbreaking for the patients who don’t qualify. I think it’s really hard to celebrate with a portion of your patients and have other patients where you know they don’t have that,” Meghan McGarry, a pulmonologist at the University of California at San Francisco, said.

Despite its limited effectiveness in terms of age, Trikafka is still truly revolutionary. It shows how modern genetics and medicine can solve problems that were previously thought impossible. Before Trikafka was announced, cystic fibrosis patients expected to die before they could even reach their mid-20s. Now, they can go to college, get a job, and raise a family. This new drug is a beacon of hope for these patients and serves as a classic textbook example of the advancements in modern medicine.