Posts tagged ‘gene therapy’
Cystic Fibrosis (CF) is the most common lethal inherited recessive disease of Caucasians. It affects approximately 1 in 2500 newborns and 50,000 individuals in total worldwide. At present, there is no cure for cystic fibrosis but life expectancy has increased with standard treatments from less than 10 years in the 1960s to an average of 30 to 40 years now.
CF affects the lungs, gut, liver, pancreas, and other tissues, but its consequences in the lungs is the most severe. CF causes the body to produce an abnormal protein a think, sticky mucus in the lungs. The dehydrated secretions prevent the body from clearing out bacteria, so this results in repeated infections and continuous inflammation and eventually leads to respiratory failure and death.
While CF causes damage to other organ tissues, most researches focus on lung cells, because they are the most common and life-threatening problems among patients. The Pseudomonas aeruginosa bacterium the most common cause of chronic and fatal lung infections for people with CF. Scientists hope to use their knowledge of this bacterium’s genetic sequence to develop innovative drugs for treating infections caused by P. aeruginosa.
CF is caused by mutation in a single gene — the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. Since the CFTR gene was identified in 1989, more than 900 mutations have been found. CFTR is a cAMP-regulated chloride channel, which opens in response to the phosphorylation of ATP. A faulty CFTR protein can not reach the apical membrane, or it has a reduced function even though it can reach the membrane. This results in impaired transport of chloride to the epithelial cells at the apical surface. The CFTR protein negatively regulates the sodium channel ENaC. Therefore, mutations in the CFTR gene leads to increase absorption of sodium ions as well. The CFTR protein also regulates many other proteins. For more detailed information, see an animated explanation of the CFTR protein here.
Gene therapy presents a hopeful treatment for CF. Scientists use a virus that causes the common cold (adenovirus) as a vector to carry normal CFTR genes to the affected cells. Since a virus enters a cell easily, it is a good vehicle for gene therapy. Another good way to transfer the normal genes is using liposomes, which are fatty substances that attach to cell surface, protecting and gene and encouraging it to enter the cell. Subsequent studies have tested other methods of gene delivery, such as synthetic vectors, nose drops or drizzling cells down a flexible tube to CFTR cells lining the airways of lungs. Researchers are now testing aerosol delivery using nebulizers.
But finding the best delivery system for transporting normal CFTR genes is only one problem that scientists must solve to develop an effective treatment for CF. Scientists must also determine the life span of affected lung cells, identify the “parent cells” that produce CFTR cells, find out how long treatment should last and how often it needs to be repeated. The amount of gene transferred is also a problem. There must be a certain number of cells that can produce the normal protein to have a theraputic effect. Furthur experiments are required to improve the efficiency of gene transfer and maintain gene expression for a longer period of time.
- UK Cystic Fibrosis Gene Therapy Consortium
- National Human Genome Research Institute: Learning about Cystic Fibrosis