Modulators are split into two classes: potentiators and correctors. Potentiators act on the CFTR ion channels that are embedded in the cell membrane, and these types of drugs help open up the channel to allow transmembrane flow. Correctors are meant to assist in the transportation of nascent proteins, a protein that is formed by ribosomes before it is morphed into a specific shape, to the cell surface to be implemented into the cell membrane.Most target the transcription stage of genetic expression. One approach has been to try and develop medication that get the ribosome to overcome the stop codon and produce a full-length CFTR protein. About 10% of CF results from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target nonsense mutations such as G542X, which consists of the amino acid glycine in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with protein synthesis and error-correction. In some cases, they can cause the cell to overcome a premature stop codon by inserting a random amino acid, thereby allowing expression of a full-length protein. Future research for these modulators is focused on the cellular targets that can be effected by a change in a genes expression. Otherwise, genetic therapy will be used as a treatment when modulator therapies do not work given that 10% of people with cystic fibrosis are not affected by these drugs.Elexacaftor/ivacaftor/tezacaftor was approved in the United States in 2019 for cystic fibrosis.
Ireland has the worlds highest prevalence of CF, at one in 1353.Although technically a rare disease, CF is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is Finland, where only one in 80 people carries a CF mutation. The World Health Organization states, "In the European Union, one in 2000–3000 newborns is found to be affected by CF". In the United States, one in 3,500 children is born with CF. In 1997, about one in 3,300 white children in the United States was born with CF. In contrast, only one in 15,000 African American children have it, and in Asian Americans, the rate was even lower at one in 32,000.Cystic fibrosis is diagnosed equally in males and females. For reasons that remain unclear, data have shown that males tend to have a longer life expectancy than females, though recent studies suggest this gender gap may no longer exist, perhaps due to improvements in health care facilities. A recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF.The distribution of CF alleles varies among populations. The frequency of ΔF508 carriers has been estimated at one in 200 in northern Sweden, one in 143 in Lithuanians, and one in 38 in Denmark. No ΔF508 carriers were found among 171 Finns and 151 Saami people. ΔF508 does occur in Finland, but it is a minority allele there.