CFTR and Cystic Fibrosis: A Need for Personalized Medicine

Abstract

Cystic fibrosis (CF), a common lethal genetic disease, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (cftr) gene, which codes for an epithelial anion channel. Although the identification of the gene in 1989 heralded hope for a therapy to treat the underlying protein defect, patients continued to be treated exclusively with drugs that address the symptoms of the disease (antibiotics for airway disease, pancreatic supplements to replace digestive enzymes, and anti-inflammatories to reduce airway inflammation) rather than treating the basic defect. Nevertheless, this approach has resulted in a marked improvement in the survival of patients with CF over the last few decades, such that the median predicted survival is now around 40 years of age. Since the discovery of the gene encoding CFTR and the identification of mutations underlying the defects in CFTR function, the hunt has been on to discover drugs that would correct the basic defect in the CFTR protein. Although almost 1900 CFTR mutations have been described in patients, they mostly fall into a few broad categories of disruption. Given the disparate ways in which CFTR mutations affect the CFTR protein however, it has become apparent that a single drug regimen will not be effective in treating all patients. Thus, a patient’s genotype would have to be taken into account when deciding which drug would be appropriate to treat individual patients with CF. Individual or personalized medicine as a concept has been increasingly highlighted in recent years, yet with CF, personalized medicine is not a mere academic exercise but rather a necessity in order to effectively treat all the mutations that are found in CF patients. This chapter presents the current CFTR mutation classifications and shows how such classification is essential in the establishment of a mutation-specific targeted drug therapy for each individual with CF.