New treatment for cystic fibrosis May 29, 2015 Latest Research Cystic fibrosis (CF) (also known as mucoviscidosis) is a common, autosomal recessive disorder. CF is a multisystem disease characterized by variable pancreatic dysfunction, chronic airway infections associated with loss of lung function and renal and hepatic disorders. This disease was first described and recognized as a genetic disorder by Andersen in 1938. Cystic fibrosis is caused by mutations in a gene in chromosome 7, which is responsible for the synthesis of cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation worldwide, found in approximately of 66% of patients with cystic fibrosis is caused by a deletion of phenylalanine in position 508 of CFTR (F508del). CFTR belongs to a family of transmembrane proteins called ATP-binding cassette transporters and its main function is to transport chloride ion in the apical membrane of cells. When this protein is missing or is dysfunctional, chloride is trapped inside the cell and NaCl is absorbed more than normally. Sticky mucus is accumulated compromising the mucociliary clearance and thus inhaled bacteria are trapped in mucus layer causing infections. CFTR is highly expressed in sinuses, lungs, pancreas, liver, gastrointestinal tract and reproductive tract. The clinical features are subdivided as below: CHRONIC AIRWAY DISEASE Chronic productive cough, airway infection, airway obstruction, nasal polyps, finger clubbing. GASTROINTESTINAL DISEASE Biliary cirrhosis, pancreatic insufficiency, pancreatitis, edema with hypoproteinemia. OTHER Salt wasting with alkalosis, infertility. The diagnosis of CF is established by clinical manifestations, a history of CF in a sibling in conjunction with laboratory evidence of CFTR dysfunction. CFTR dysfunction is diagnosed by elevated sweat chloride and genetic test. A sweat chloride concentration greater than 60mmol/L on repeated analysis is diagnostic for CF. Treatment of cystic fibrosis is complicated and is multidisciplinary. The symptomatic treatment is based on airway clearance, treatment of airway infections and treatment of the symptoms of other organs that this disease may affect. Treatments that are effective against one CF mutation often do not help with others. A new treatment is announced in the New England Journal of Medicine for the F508del mutation, which is the most frequent mutation in CF. This treatment doesn’t only treat symptoms but the underlying cause of the disease. This treatment involves the combination of two existing drugs Lumacaftor and Ivacaftor. Ivacaftor is already being used for treatment of CF, but for only one form of mutation. This drug opens CFTR channels so that chloride can be transported more easily. Lumacaftor potentially increases the proteins on the surface of the cells so that there are more chloride channels. Two double blind studies were conducted with cystic fibrosis patients given either a combination of the two drugs or a placebo over a 24-week period. Acute symptoms were reduced 30-40% in patients who were in drug combinations; on the other hand patients on placebo were more likely to be hospitalized or to need intravenous antibiotics. This new treatment may extend lifespan and gives a better quality of life to these patients until a cure for CF is found!! REFERENCES: http://discovermagazine.com/2013/september/14-doorway-to-a-cure http://learn.genetics.utah.edu/content/disorders/singlegene/cf/ http://www.nejm.org/doi/full/10.1056/NEJMoa1409547#t=articleBackground http://www.iflscience.com/health-and-medicine/success-against-most-common-form-cystic-fibrosis Post Views: 1,986 Leave a Reply Cancel ReplyYou must be logged in to post a comment. This site uses Akismet to reduce spam. Learn how your comment data is processed.