Cystic fibrosis – new therapeutic aproaches

Abstract

Introduction: In the 1970s, the monogenic autosomal recessive disease cystic fibrosis (CF) was deadly in childhood. In the 1990s, symptomatic treatment and comprehensive multidisciplinary follow up in CF centers have allowed most patients to live to young adulthood. New and innovative therapies emerged following the discovery of the CF gene in 1989. and unraveling the impact that different mutations exert on the structure and function of the gene product, the so-called the chloride channel. Areas covered:This is a review of new therapeutic approaches focusing mainly on CFTR (cystic fibrosis transmembrane regulator) modulators that are adopted into standard care in many countries, including Croatia at the end of year 2021. Modulators are small molecules that restore the expression and functionality of the chloride channel by changing cell-processing, folding and stability of the mutant CFTR. Modulators target proximal events in the disease pathogenesis, they complement standard care and are potentially applicable for 90% of the people with CF. Effects of treatment include better lung function, less pulmonary exacerbations, better nutritional status and most importantly increased survival, especially for patients starting therapy early in childhood. Other novel approaches, such as gene therapy and activation of alternative ion channels to bypass CFTR are in early stages of development. Cell models from patient-derived specimens with different mutations allow ex vivo evaluation of CFTR function and testing therapeutic effects of different substances. These models can thus be used for personalized medicine in CF. Conclusion: Effective CFTR modulators deeply modify the disease course, improve the quality of life and survival in CF. These drugs bring enormous promise for the immediate future, heralding an era in which therapeutic choices are driven by personalized genetic information.