Cystic Fibrosis
The Molecular Biology behind the Disease and its Treatment
A look at the molecular biology behind cystic fibrosis, it's pattern of inheritance and the prospects of future gene therapy.
Cystic fibrosis (CF) is a chronic, progressive disease which currently leads to a reduced life expectancy. CF principally affects the respiratory and digestive systems in children and young adults. The sweat glands and the reproductive system are also usually involved.
CF is caused by mutations in a large gene that encodes a large protein called the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR protein is found in cell membranes, its role to transport chloride ions out of the cell.
People who have inherited only one copy of the mutated gene have no symptoms of the disease. Two mutated genes must be present for CF to appear. This means that if both parents are CF carriers (they both have one copy each of the mutated gene), their children would only show CF symptoms if they had inherited both faulty copies of the CFTR gene, one from each parent.
When the CFTR gene is mutated, it either produces a CFTR protein that does not work or as in a large number of cases, there is no CFTR protein produced at all. When there is no CFTR protein present this is because part of the DNA code in the CFTR gene is missing, making the CFTR protein shorter than normal. The cell’s quality control system destroys the CFTR protein, as it is too short.
CF affects different people in different ways and to varying degrees. Although in all cases, they have the same basic problem, an abnormality in the glands that produce or secrete sweat and mucus. Sweat is needed to cool the body; mucus is needed to lubricate the respiratory, digestive, and reproductive systems and preventing them from drying out and from becoming infected.
Cystic fibrosis treatment
CF sufferers require a number of varying treatments. People with CF need daily chest physiotherapy, regular courses of antibiotics and vaccinations. Most CF sufferers need to take pancreatic enzymes with their meals to help them digest their food.
Gene therapy
Research is being carried out on gene therapy for CF. If gene therapy were successful it would correct the genetic defect that causes CF, rather than only treating the symptoms. Scientists would have to be able to add enough normal genes to the airways of a CF sufferer to correct the faulty cells.
Clinical trials have shown that the normal gene can be safely transferred into the airways of CF sufferers. Scientists are now working to develop more efficient delivery methods. These delivery methods include modified viruses that could carry the gene into the airways. For example, scientists first used a modified adenovirus (the cold virus) to carry normal genes directly into the damaged CF airway cells. Scientists delivered the adenovirus as nose drops, or drizzled down a bronchoscope to reach the CF cells lining the airways. Ideally, the healthy gene could be inhaled or injected.
Scientists are currently concentrating on developing gene therapy for the airway cells as these cells are easily accessible and because lung damage due to CF is the most common life-threatening problem. However the scientists are hopeful that some of the same technology being developed for gene therapy to treat the lungs of CF sufferers will eventually be adapted to treat other organs affected by CF, such as the pancreas.
Sources:
Genetic Disease Profile: Cystic Fibrosis – Gene Gateway – Exploring Genes and genetic disorders
Gene Therapy and CF – Cystic Fibrosis Foundation
