title: Novel personalized therapies for cystic fibrosis: treating the basic defect in all patients.
abstract: Cystic fibrosis (CF) is the most common genetic life-shortening condition in Caucasians. Despite being a multi-organ disease, CF is classically diagnosed by symptoms of acute/chronic respiratory disease, with persistent pulmonary infections and mucus plugging of the airways and failure to thrive. These multiple symptoms originate from dysfunction of the CF transmembrane conductance regulator (CFTR) protein, a channel that mediates anion transport across epithelia. Indeed, establishment of a definite CF diagnosis requires proof of CFTR dysfunction, commonly through the so-called sweat Cl(-) test. Many drug therapies, including mucolytics and antibiotics, aim to alleviate the symptoms of CF lung disease. However, new therapies to modulate defective CFTR, the basic defect underlying CF, have started to reach the clinic, and several others are in development or in clinical trials. The novelty of these therapies is that, besides targeting the basic defect underlying CF, they are mutation specific. Indeed, even this monogenic disease is influenced by a large number of different genes and biological pathways as well as by environmental factors that are difficult to assess. Accordingly, every person with CF is unique and so functional assessment of patients' tissues ex vivo is key for diagnosing and predicting the severity of this disease. Of note, such assessment will also be crucial to assess drug responses, in order to effectively treat all CF patients. It is not because it is a monogenic disorder that personalized treatment for CF is much easier than for complex disorders.
authors.affiliation: BioFIG-Center for Biodiversity, Functional and Integrative Genomics, Faculty of Sciences, University of Lisboa, Lisboa, Portugal.
authors.forename: M D
authors.initials: MD
authors.lastname: Amaral
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use; D000627:Aminophenols / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D018389:Codon, Nonsense; D003550:Cystic Fibrosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D019317:Evidence-Based Medicine; D016368:Frameshift Mutation; D019833:Genistein / Q000627:therapeutic use; D006801:Humans; D010069:Oxadiazoles / Q000627:therapeutic use; D010641:Phenotype; D057285:Precision Medicine; D058914:Purinergic Antagonists / Q000627:therapeutic use; D015363:Quinolones / Q000627:therapeutic use; D035583:Rare Diseases; D012720:Severity of Illness Index; D013545:Sweat Glands / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000627:Aminophenols; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018389:Codon, Nonsense; D010069:Oxadiazoles; D058914:Purinergic Antagonists; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D019833:Genistein; C515878:ataluren
keywords: monogenic disorder; mutation-specific therapies; personalized therapy; rare diseases