The science behind the development of the new generation of medicines

Dr Janet Allen, CF Trust Director of Research, explains the science behind the development of the new generation of medicines targeting the basic defect in cystic fibrosis.

Exciting new work presented at the NACFC reveals the science behind the search for more effective drugs to treat the commonest genetic mutation in cystic fibrosis (F508del). 

The CF gene provides instructions for making a protein called CFTR (cystic fibrosis transmembrane conductance regulator). This protein controls the movement of salt and water in and out of the cells within the body.

Depending on which mutation is present in the gene, the CFTR protein is either missing or doesn’t work properly. In those with the F508del mutation, the CFTR protein is misshapen and the body removes it (the protein must fold into very complex shapes to work in cells and act as a channel.)  So, CFTR is effectively absent in this mutation.

At the meeting today, scientists showed that the F508del mutation affects the folding of the protein through two separate mechanisms and both need to be corrected to allow the channel to fold correctly.  This detailed understanding of the basic mechanisms of the folding pathway permits the development of sophisticated new ways to search for drugs that will be more effective in correcting it. 

This study shows the critical role that basic science has in generating the next generation of drugs.