Cystic fibrosis is one of the most common fatal genetic diseases with around 70,000 people worldwide affected. A mutation in the cystic fibrosis gene (CFTR – cystic fibrosis transmembrane conductance regulator) is the sole cause of the disease. Cystic fibrosis is typically indentified as a disease affecting the lungs but it can impact multiple organs in the body including the pancreas, liver, kidneys, and intestines. Long term complications of the disease include difficulty breathing, frequent lung infections, poor growth, and even infertility or death. There is no cure for cystic fibrosis and with proper diagnosis and treatment people with the disease have a life expectancy between 37 to 50 years. The majority of deaths due to cystic fibrosis are caused by problems with the lungs. Scientists have known about the existence of the gene responsible for cystic fibrosis for over 25 years but there has been little advancement in the treatment of the disease beyond the use of antibiotics and lung transplantation. This is primarily because up till now, we have had no way of fixing or aiding the mutated protein. All of that may be about to change however with the results of a recent clinical trial published in the Lancet Respiratory Medicine.
The clinical trial looked at the use of gene therapy to treat and improve the lung function of people with cystic fibrosis. There are a couple things to explain before we get into the results.
- Gene therapy has been touted as the cure for all our genetic disorders since it was first conceptualized in the early 1970’s. For the most part it has failed to impress primarily because of problems with delivery and uptake of the gene. In order for gene therapy to be effective, its payload (the gene) needs to be delivered to as many affected cells as possible. This can be troublesome because of the sheer number of cells in a target organ.
- The outcome measure of this study was lung function. Your lung’s job is to bring in air from your environment to oxygenate your blood. Normally it performs this function well, however, in diseases like cystic fibrosis or asthma, the process of bringing in or expiring air can be decreased. This decrease in the ability move air in and out of your lungs causes a decrease in lung function. Lung function can be measured by recording the amount of air someone can force out of their lungs in one second (called FEV1).
The researchers in this trial gave patients with cystic fibrosis either the treatment containing a working copy of the CFTR gene or a placebo. The CFTR gene was delivered through an inhaler every 28 days for a year. The gene was delivered to the cells through a lipid bubble carrier called a liposome. The patients had their lung function measured every treatment visit for the year. At the end of the trial, it was found that the people who were given the gene therapy treatment had 3.7% better lung function in than the placebo group. While this may not sound like a lot, the results could be quite important when considering the natural progression of cystic fibrosis. The lung function of people with cystic fibrosis decreases by 2-3% every year until their lungs eventually don’t work anymore. This means the gene therapy treatment halted the decrease in lung function over a year typically seen in cystic fibrosis. While the treatment did not increase the lung function of these people, in combination with other therapies this could still prove to be a valuable outcome.
These results should be taken cautiously. There is still plenty of work to be done before this is called the silver bullet cure for cystic fibrosis. The treatment did not help with the excess mucus that people with cystic fibrosis have. Nor did it help with the symptoms people report. The mucus may actually have been causing trouble getting the drug to the appropriate areas of the lung because it acts as a plug in the airways. It remains to be seen if these benefits remain after one year or even after the treatment is removed. However, the results of the trial suggest that a person on this treatment would need a transplant at a later age rather than in their late 20’s.