Cystic fibrosis and α1-antitrypsin deficiency are the two most common inherited lung diseases, and both of them happen to be caused by a known, single gene mutation. A study conducted at Boston University’s School of Medicine and recently published in the Journal of Clinical Investigation describes a protocol in which gene therapy was used to treat emphysema in mice models.
Emphysema creates an increase in alveolar compliance, a measurement of how the volume changes in response to a change in pressure, V/P. In other words, lung tissue begins to lose its integrity and become a lot more stretchy with less elastic rebound. This sounds like a good thing (since it seems that it would be easier inhale with lungs which have less resistance); however, emphysema’s real problem is in exhalation. Patients who seem to be gasping for air are actually having trouble clearing their lungs (since there’s less rebound).
In the case of α1-antitrypsin deficiency, the immunological protection provided by macrophages in the respiratory tract (ie, the protease trypsin) is unable to be “neutralized” by other substances (like antitrypsin). Consequently, the active protease ultimately begins to self digest the delicate respiratory tissues leading to emphysema.
Now researchers are targeting these macrophages for gene therapy. Gene therapy involves taking a “good” gene, using a vector (usually a virus) to carry it into a host cell, and then have that cell successfully express the protein coded for by the gene. For example, the scientists at Boston University’s School of Medicine used a lentivirus to introduce a functional version of the antitrypsin gene into mice with the deficiency.
Lung tissue is particularly easy to transfect since viral vectors can easily access the entire tracheobronchial tree through inhalation, and this is exactly what researchers took advantage of. The problem was ensuring that the gene expression lasted as long as possible, so transfecting the stem cell line was a potential possibility. Read more about it by clicking on the link above!
So this is just another application of gene therapy. One day, humans will probably have synthetic plasmids containing the insulin gene (for type I diabetes patients), antitrypsin (for α1-antitrypsin), the CFTR gene (for cystic fibrosis patients), etc. Pretty exciting years coming up for medicine! 🙂