The genetic disease that we know today as cystic fibrosis (CF) has been recognized for centuries, with references found in medical texts dating to the late 1500s. Earlier suggestions of the disease go back to the Middle Ages, when a Germanic description of its symptoms was written as: “Wehe dem Kind, das beim Kuss auf die Stirn salzig schmeckt, es ist verhext und muss baldsterben” — “Woe to the child who tastes salty from a kiss on the brow, for he is hexed, and soon must die.” Saltiness was, in fact, the key that led to development of the first test for the disease 60 years ago. Known simply as a “sweat test,” it remains the gold standard for confirming a diagnosis of CF.
The outlook for patients with CF has improved dramatically since those earlier times. In the 1950s, the median survival age for patients with CF was 2. By 1962, the predicted median survival was about 10 years, according to the National Institutes of Health. But today, with newborn screening to detect the disease early, mechanical therapy to loosen thickened mucus and help patients to expel it from their lungs, improved antibiotics, nutritional enhancement and digestive enzymes, and a new classification of groundbreaking drugs that correct genetic mutations of the disease, the median survival age in the United States is 47 years old.
“With the advent of CFTR (cystic fibrosis transmembrane conductance regulator) therapy to treat the disease, we have seen a significant increase in the mean age of CF patients in the United States,” says pediatric pulmonologist Marlyn S. Woo, MD, director of the UCLA Mattel Children’s Hospital Cystic Fibrosis Center.
This new CFTR therapy, which is designed to correct the malfunctioning protein in the CF gene that regulates the flow of water and chloride in and out of cells in the lungs and other organs, has meant substantial improvement for 46 percent of CF patients with a specific genetic mutation. Because there are several variations in the mutation of the CF gene, the therapy currently is not beneficial for all patients. But researchers believe that a new triple-drug combination therapy that will be submitted to the U.S. Food and Drug Administration for approval this year offers hope for an effective therapy for 90 percent of CF patients.
“These are not ultimate cures — they can’t undo the damage that’s already been done — but they are very effective treatments for certain patients to keep the disease in check,” Dr. Woo says.
In addition, a recently developed process, called theratyping, to match medications with mutations will enable more patients with rare mutations to benefit from modulators.
When Dr. Woo first began working with CF patients, in the early 1980s, the median survival age was 14 years old, she says. “Really, the only thing we had to offer to them was albuterol. They were trying prednisone — which wasn’t doing much for those patients — and there was a powdered form of pancreatic enzyme. That was about it,” she says. “They had already started CF specialty care centers, but there just wasn’t much we could do for them other than try to feed them a lot to get their weight up and give them oral or intravenous antibiotics. Nothing at that point was effective in treating the disease itself.”
While greater emphasis on nutrition and improvements to methods for airway clearance were important steps forward, the game-changer in CF treatment was, Dr. Woo says, the advent in the late 1980s and early 1990s of CF-specific medications to thin accumulated mucus in the lungs and reduce the risk of infections. “If we look back on the history of cystic fibrosis, that, coupled with the development of antibiotic therapy and better pancreatic enzymes has been the single biggest advance to significantly increase the lifespan of our patients, and it also to slow the progression of the disease,” she says.
With these medical advances and increases in life expectancy, CF no longer is limited to children. More than half of CF patients in United States now are over the age of 21, and this population has specialized needs. At UCLA, the Adult Cystic Fibrosis Program is led by director Patricia H. Eshaghian, MD, and associate director David Sayah, MD, PhD; Dr. Sayah was Kathlyn Chassey’s physician when she was hospitalized at UCLA for her lung transplant.
Will there be a cure for CF? Dr. Woo believes one will come within the next 10 years. “It may not come about from correcting the protein or getting the protein to function; it may come from some other direction. But I believe that it will come,” she says. “We are very close.”
— David Greenwald
