In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis
Year: 2019
Type: article
Abstract: animals showed the greatest VX-770-mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, glucose tolerance, growth and survival, and to reduced mucus accumulation and bacterial infections in the lung. VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidity occurring when withdrawal was initiated during the first 2 weeks after birth. The results suggest that CFTR is important for establishing organ function early in life. Moreover, this ferret model provides proof of concept for in utero pharmacologic correction of genetic disease and offers opportunities for understanding CF pathogenesis and improving treatment.
Source: Science Translational Medicine
Authors: Xingshen Sun, Yaling Yi, Ziying Yan, Bradley H. Rosen, Bo Liang, Michael C. Winter, T. Idil Apak Evans, Pavana G. Rotti, Yu Yang, Jaimie S. Gray, Soo Yeun Park, Weihong Zhou, Yulong Zhang, Shashanna R. Moll, Lisa Woody, Dao M. Tran, Licong Jiang, Annelotte M. Vonk, Jeffrey M. Beekman, Paul Negulescu, Fred Van Goor, Dennis F. Fiorino, Katherine N. Gibson-Corley, John F. Engelhardt
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Cystic Fibrosis Foundation, Vertex Pharmaceuticals, ZonMw, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: G1087311284, The University of Iowa Clinical and Translational Science Award, Gene Therapy For Cystic Fibrosis Lung Disease, G2593938437, G2716248383, G3107428936, G336615015, G5798220538, Splanchno-Hormonal Mechanisms of Cystic Fibrosis Related Diabetes, G8096217485, Ultra-low Dose, High Speed, High Resolution, Multispectral, Multi-Source MDCT Sca, Environmental Health Sciences Research Center, Precision Medicine Center for Cystic Fibrosis
OpenAlex ID: W2924613492