101. One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies
- Author
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Marianne Carlon and Marjolein Ensinck
- Subjects
NUCLEOTIDE-BINDING DOMAIN ,Cystic Fibrosis ,Cystic Fibrosis Transmembrane Conductance Regulator ,PREMATURE TERMINATION CODONS ,DOUBLE-BLIND ,SMALL-MOLECULE CORRECTORS ,DELTA-F508 CFTR ,Humans ,translational readthrough inducing drugs (TRIDs) ,NMD inhibition ,Ion Transport ,Science & Technology ,MESSENGER-RNA DECAY ,CHLORIDE TRANSPORT ,proteostasis modulation ,EPITHELIAL-CELLS ,General Medicine ,Genetic Therapy ,Cell Biology ,personalized medicine ,CFTR modulators ,gene therapy ,TRANSMEMBRANE CONDUCTANCE REGULATOR ,stabilizers ,CFTR MEMBRANE EXPRESSION ,Mutation ,cystic fibrosis transmembrane conductance regulator (CFTR) ,amplifiers ,Life Sciences & Biomedicine ,cystic fibrosis (CF) - Abstract
Cystic fibrosis (CF) is the most common monogenic disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Over the last 30 years, tremendous progress has been made in understanding the molecular basis of CF and the development of treatments that target the underlying defects in CF. Currently, a highly effective CFTR modulator treatment (Kalydeco™/Trikafta™) is available for 90% of people with CF. In this review, we will give an extensive overview of past and ongoing efforts in the development of therapies targeting the molecular defects in CF. We will discuss strategies targeting the CFTR protein (i.e., CFTR modulators such as correctors and potentiators), its cellular environment (i.e., proteostasis modulation, stabilization at the plasma membrane), the CFTR mRNA (i.e., amplifiers, nonsense mediated mRNA decay suppressors, translational readthrough inducing drugs) or the CFTR gene (gene therapies). Finally, we will focus on how these efforts can be applied to the 15% of people with CF for whom no causal therapy is available yet. ispartof: CELLS vol:11 issue:12 ispartof: location:Switzerland status: published
- Published
- 2022