Genetic mutation, biochemical defect, disease and therapy: Cystic fibrosis: From bench to bedside

Cystic fibrosis is one of the most common hereditary caucasian diseases. Ge ne frequency ranges between 1 : 20 to 1 : 25. The gene defect is located on chromosome 7 and the gene codes for a transmembrane protein, CFTR (cystic fibrosis transmembrane conductance regulator), which is involved in chlorid e secretion. Functional impairment leads to changes in electrolyte concentr ations of different body fluids. in the liver CFTR is expressed in the bili ary epithelial cells. Mutations lead to impairment of bile secretion with c onsecutive liver damage. New therapeutic challenges try to restore transmem brane chloride fluxes. one is ursodeoxycholic acid (UDCA) which activates c alcium dependent chloride channels. However, only gene therapy is able to r estore CFTR function. The selective gene application to the liver is far fr om being practicable. An expanded form of gene therapy however; liver trans plantation, has clinical success. Basic research has improved our knowledge about cystic fibrosis and has bro ught us new therapeutic options. For the liver most of these options are st ill experimental.