A year after researchers cast a new light on the odd way a cystic fibrosis drug called ivacaftor works to treat a rare form of the inherited disease, a newer study could help increase its efficacy still further. Much of the harm from cystic fibrosis is due to mucus collecting in the airway, which makes breathing difficult and leads to infection. There are several gene mutations that can cause this, and for patients with one particular mutation, ivacaftor restores breathing—but doctors did not, at first, understand precisely what effect it had or exactly how it worked.
Cystic fibrosis involves a protein called CFTR that regulates the transport of ions into and out of cells using a molecule called adenosine triphosphate, or ATP. CFTR provides a channel for ions to pass through, and ATP is ordinarily the key that unlocks the protein and allows ions to go through. When one of the mutations that causes cystic fibrosis occurs, this system doesn’t work properly. Initially researchers believed that, in patients with a particular mutation, ivacaftor could substitute for ATP at the same receptor site and unlock the channel in the same way. What the researchers last year found, however, was that the drug actually works at a different site and works more like a back door. That means it may be effective in patients with several types of mutation.
Indeed, that is what the study earlier this year found. Patients with a different, more recently discovered type of cystic fibrosis mutation were also helped by ivacaftor, despite this mutation causing a different malfunction in the way ATP and CFTR interact. ATP opens the channel by carrying energy to the protein, researchers found, not by being consumed as they had originally thought, and this discovery suggests ivacaftor might simply work a similar way.
Cystic fibrosis affects about 30,000 children and adults in the United States, with about 1,000 new diagnoses every year. It shortens a patient’s lifespan, with about half of patients not making it to 40. Ivacaftor is so far the only treatment that addresses the root causes of the condition, but medical treatments and physical therapy can help alleviate the symptoms, with bronchodilators and mucus-thinning medications available to help patients breathe and surgery, if necessary, to create long-term improvement.