In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis.

ABSTRACT: Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. To address this issue, we generated ferrets harboring a VX-770 (ivacaftor)-responsive CFTR ^G551D mutation. In utero VX-770 administration provided partial protection from developmental pathologies in the pancreas, intestine, and male reproductive tract. Homozygous CFTR ^G551D/G551D animals showed the greatest VX-770-mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, g

SUBMITTER: Sun X 

PROVIDER: S-EPMC6489481 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature