Cystic fibrosis (CF) is a rare, life-limiting genetic disease that affects your ability to breath.
CF causes thick mucus to build up in the lungs, digestive tract, and other parts of a person’s body. That mucus damages the organs, leading to decreased lung function, lung infections, digestive problems. CF patients also often have complications like diabetes and liver damage.
Without treatment, it can lead to malnutrition, severe damage to the lungs with eventual respiratory failure, and shortened life expectancy. CF is the most common genetic disorder in Caucasians, affecting about 30,000 patients in the United States and 70,000 worldwide. However, it also occurs in Hispanics, African Americans, and some Native Americans.
How is cystic fibrosis inherited?
A recessive genetic disease, a mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene causes cystic fibrosis. That means that both parents must be CF carriers for the baby to develop the disease. There are thousands of different mutations of this gene, each having a different name like F508del.
“Back in 1989, when the CFTR gene was linked to cystic fibrosis, a specific mutation, F508del (delta508F), was thought to be the only mutation. Now we know that although the F508del mutation is the most common, approximately 2,000 different mutations in CFTR have been identified to date which can affect the course of cystic fibrosis in a patient,” says Dr. Andrew Colin, professor of cystic fibrosis and pediatric pulmonology; and Director of Pediatric Pulmonology at the University of Miami Miller School of Medicine. The CFTR gene produces the CFTR protein that aids in the movement of chloride (a component of salt) out of cells, he says.
In the U.S., all 50 states test newborn babies for cystic fibrosis, so doctors diagnose it before clinical symptoms set in. They place a few drops of blood from a heel prick on a Guthrie card. Then the hospital or clinic sends the cared to a specialized state laboratory that does genetic testing. Infants who test positive on the newborn screening test have additional testing to confirm whether they have cystic fibrosis and which of the CFTR-related genetic mutations are present.
Another way that doctors diagnose CF is through a sweat test that measures the amount of chloride in the blood.
How does the CFTR protein work?
To simplify, the protein ensures that there is the right balance of salt and water in the body. It does this by traveling to the surface of your cells and creating a “channel” that allows for transferring chloride and water. When it functions properly, it ensures proper hydration of the cells in our organs.
When it doesn’t, it throws the balance of salt and water off, and mucus builds up that blocks passages in organs like the pancreas and the lungs. These changes lead to lung damage and, eventually, respiratory failure. In the pancreas, poor digestion, absorption, and malnutrition occur. Other organ-specific problems vary among patients.
Here is where the specific CFTR mutation comes into play.
Dr. Colin says that children who inherit two copies of the F508del mutation have one of the most severe forms of the disease. That combination makes the pancreas unable to produce the digestive enzymes the body needs to process food, which leads to malabsorption of critical nutrients and malnutrition. In the early days of the disease, malnutrition, and starvation usually led to death. Current treatment compensates for this problem by supplementing the diet with the missing pancreatic enzymes. Children who inherit different gene mutations have milder forms of the disease. We now have a better understanding of mutations that predict pancreatic insufficiency.
The extent and progression of lung disease are not as predictable. In these patients, the thick mucus in the lungs is a breeding place for bacteria that cause stubborn life-threatening infections. Lung infections, and specifically the nature of the bacteria that underlie the infection, dictate the outcome of cystic fibrosis patients. CF patients are living longer, so they have exposure to antibiotics for long periods and build up antibiotic resistance.
“In South Florida, we have some new types of bacteria we are finding in CF lungs that are very aggressive and hard to fight,” says Dr. Colin.
The FDA recently approved a new treatment.
Trikafta is a therapy that the FDA recently approved for patients carrying the most common CF gene mutation, F508del. It is a combination of three drugs that do multiple jobs. Two of the medicines salvage defective protein while the third drug activates it to do its job. Trikafta is approved for patients 12 years and older with cystic fibrosis who have at least one F508del mutation, about 90 percent of the cystic fibrosis population. More research will reveal whether patients with other mutations could benefit.
The studies leading to FDA approval of Trikafta showed dramatic results. The effect of the new drug was almost immediate and persisted. While the current approval is for children age 12 and up, Dr. Colin expects that the ongoing research will bring about approval for children as young as six within the next six months.
Clinical trials are ongoing.
“Both the Adult and Pediatric CF Programs at UM are part of the Therapeutic Development Network (TDN) of the CF Foundation. We are one of 92 CF Foundation-accredited care centers that engage in clinical research. There are 30 research protocols of drugs at various stages of development, of which Trikafta represents the most recent completed study. We select study participants from amongst our patients and conduct clinical trials,” explains Dr. Colin. You can find more information about UHealth clinical trials here.
Mary Jo Blackwood, RN, MPH, is a contributing writer for UMiami Health News. Based in St. Louis, MO, and Colorado, she has written medical articles and webpages for consumer publications and major university health centers.
LEARN MORE: Biologics: a revolutionary drug treatment