Cystic Fibrosis Research
Cystic fibrosis (CF) is a common inherited disease that mostly affects the lungs and airways of a sufferer. It is caused by mutations in the gene for the CF transmembrane conductance regulator (CFTR), a phosphorylation-regulated chloride channel. One of the main pathological characteristics of CF is the failure of airway defence against bacterial infection, leading to frequent chest infection and progressive lung damage.
Cystic Fibrosis Research Product Areas
In CF the airway surface fluid (more commonly known as 'mucus') is thicker and has a reduced liquid volume (dehydrated). Thicker secretions are also seen from the pancreas, consequently also affecting the digestive system by blocking the passage of pancreatic enzymes into the gut.
The CFTR is located in the apical membrane of lung epithelia and the loss of CFTR channel function leads to abnormal transepithelial salt and fluid transport and concentration. CF sufferers present with mucus containing higher Cl- and Na+ compared to healthy subjects due to defective cAMP-dependent Cl- secretion and increased airway Na+ absorption caused by the CFTR mutation. This high salt concentration can prevent bacteriocidal activity on the epithelia, leading to an increased chance of infection, most commonly by the bacteria Pseudomona aeruginosa or Staphylococcus aureus. Infection leads to an inflammatory response in CF airways, which over time can become exaggerated and promote lung damage.
Therapeutics agents for treatment include potentiators of the defective CFTR protein such as Ivacaftor, blockers of Na+ transport, inhaled corticosteroids, antibiotics and bronchodilator drugs. As CF is a caused by a gene mutation, gene therapy and antisense oligonucleotide (ASO) to correct the defective gene are also being explored. Lung transplantation is occasionally required in the most severe cases.