Cystic Fibrosis Treatment; Overview of Small Molecule Modulators and Genetic Therapy

Abstract

Cystic fibrosis, CF, is a life-shortening genetic disease affecting Caucasian population. It is a recessive genetic disease  that is mainly caused by different types of mutations affecting the gene encoding for the cystic fibrosis transmembrane  conductance regulator, CFTR, protein. A malfunctioning CFTR protein would lead to the accumulation of a thick viscous  mucous layer blocking pancreatic ducts, intestines and airways which is the primary reason of death. Treatment of cystic  fibrosis was mainly addressing the symptoms to overcome the complications of the disease. Since the early 2010s,  the development of an actual therapy has reached great milestones including small molecule modulators and genetic therapy. Small molecule therapy depends on the development of small pharmacological agents that can, through different mechanisms, restore the function of the mutated CFTR protein. On the other hand, gene-editing techniques are evolving showing very promising results. Gene therapy entails the relocation of a proper copy of the  CFTR gene in the aim of expressing a functional CFTR protein. Interesting advances in the development  of small  molecule and genetic therapies are discussed in this review article with a highlight on their benefits and limitations.