Cystic fibrosis: Physiopathology and the latest pharmacological treatments. (December 2020)

• Record Type: Journal Article
• Authors: Fonseca, Carla; Bicker, Joana; Alves, Gilberto; Falcão, Amílcar; Fortuna, Ana
• Is Part Of: Pharmacological research. Volume 162(2020)
• Publication Date: 2020-12
• Subjects: AA arachidonic acid -- AAV2 adeno-associated virus serotype 2 -- ABC ATP-binding cassette -- AMPK AMP-activated protein kinase -- ANO1 anoctamin-1 -- ASO antisense oligonucleotide -- ATP adenosine triphosphate -- cAMP cyclic adenosine monophosphate -- CF cystic fibrosis -- CFTR cystic fibrosis transmembrane conductance regulator -- Cl− chloride anion -- DIOS distal intestinal obstruction syndrome -- DNA deoxyribonucleic acid -- ENaC epithelial sodium channel -- FEV1 forced expiratory volume in 1 s -- IKBKB inhibitor of IKKβ -- IKKβ IkB kinase -- IL-8 interleukin 8 -- K+ potassium cation -- LA linoleic acid -- miRNA microRNA -- mRNA messenger RNA -- Na+ sodium cation -- NBD nucleotide-binding domain -- NF-kB nuclear factor kappa B -- PKA protein kinase A -- RNA ribonucleic acid -- TM transmembrane -- TMD transmembrane domain -- TOM1 target of Myb1 -- TSB target site blocker -- UTR untranslated regions; Amiloride (PubChem CID:16231) -- Azithromycin (PubChem CID:447043) -- Aztreonam (PubChem CID:5742832) -- Benzamil (PubChem CID:108107) -- Ibuprofen (PubChem CID:3672) -- Ivacaftor (PubChem CID:16220172) -- Lumacaftor (PubChem CID:16678941) -- Phenamil (PubChem CID:135403792) -- Tezacaftor (PubChem CID:46199646) -- Tobramycin (PubChem CID:36294); Cystic fibrosis -- CFTR -- CFTR modulators -- Biotechnology -- Inhalation; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105267
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease, caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which primarily affects the lungs and digestive system . This gene encodes the CFTR protein, a distinctive membrane transporter of the ATP-binding cassette (ABC) superfamily. It functions as a chloride channel, allowing the balance and transport of chloride through the apical membrane of epithelial cells. Due to its ubiquitous location, mutations in the CFTR gene trigger multiple changes in ion transport and metabolic pathways, affecting various organs, as it will be herein explained. Pulmonary impairment is the most characteristic comorbidity of CF and respiratory failure is the main cause of death. This review presents the importance of an early diagnosis of CF to establish, as soon as possible, a primary therapy for symptomatic prevention and relief. It also mentions new therapeutic approaches that include CFTR modulators. They are correctors and/or potentiators of the deficient CFTR channel. In an attempt to overcome the disadvantages of CFTR modulators, the application of biotechnology techniques is addressed, such as gene therapy, gene editing, RNA therapy and therapeutic microRNAs. The potential of the intranasal administration route is another presented aspect.