A new discovery made by researchers at University of North Carolina can improve respiratory function of patients with COPD and cystic fibrosis. The study, published online in The FASEB Journal, shows that “SPLUNC1” protein that can diminish airway obstruction by inhibiting epithelial sodium channel (ENaC).
Researchers created a synthetic peptide from SPLUNC1 that is able to inhibit the epithelial sodium channel. To realize what part of SPLUNC1 is basically inhibiting sodium channel, researchers have gradually fragmented this protein. After fragmented 85% of protein, they have realized that the inhibitory function lies in the other 15% and created a synthetic peptide similar to the region. Subsequently, they tested to see whether this peptide inhibits sodium channel. The results were positive: SPLUC1 synthetic peptide blocked ion channel function and fluid absorption. Also, studies have shown that SPLUC1 can be used as treatment in cystic fibrosis. Robert Tarran, Ph.D., a researcher involved in the work from the Cystic Fibrosis/Pulmonary Research and Treatment Center at the University of North Carolina in Chapel Hill, said that the study may lead to a new treatment that can help reverse the mucus dehydration seen in Cystic Fibrosis and COPD patients.
Cystic fibrosis is a hereditary condition affecting the lungs, pancreas, liver and sinuses. Characteristic to cystic fibrosis is mutation ?F508 of CFTR gene. CFTR gene encodes a protein responsible for the transport of ions through the skin epithelium. Normal CFTR inhibits sodium channels, while the mutant CFTR let the sodium channel uninhibited. In other words, sodium absorption is increased. Also, due to mutant CFTR, chloride is secreted. Therefore, one of the diagnostic test is sweat test. Cystic fibrosis patients have high amounts of sodium and chlorine in their sweat. Because of alterations in epithelial ion transport, mucus secreted by exocrine glands is extremely viscous, causing the obstruction of excretory channels.
As far as the lung is concerned, cystic fibrosis is associated with hyperinflation, bronchiectasis, diffuse fibrosis and atelectasis due to mucus plugs. Also, another sign is the presence of nasal polyps, which, after surgical excision, have high rate of recurrence. In addition, respiratory function is affected by frequent infections. The most frequently infections are those caused by Staphyloccocus aureus, Pseudomonas aeruginosa, Hemophilus influenzae, and Burkholderia cepacia. Pancreatic insufficiency is another marker of the disease. Due to the blockage of the pancreatic duct, pancreatic enzymes can not be discharged into the duodenum and this leads to pancreatitis. A consequence of pancreatic insufficiency is malabsorbtion . This creates shortages of vitamins A, D, E and K. There are other conditions associated to cystic fibrosis, such as primary biliary cirrhosis, diabetes or infertility. It is not a curable disease, but there are many treatments that alleviate symptoms.