Researchers from Boston University School of Medicine (BUSM) have discovered a new gene therapy that may prevent the progression of emphysema. The study, published online in the Journal of Clinical Investigation, describes a method of treatment that will express therapeutic genes in lung tissues over a lifetime after a single treatment.
The genetic mutation of Alpha-1 Anti-trypsinis, and subsequent deficiency, is the most commonly inherited form of emphysema seen in young people. It predisposes affected individuals to early emphysema and cirrhosis of the liver.
According to researchers, gene transfer into specific cell lineages in vivo remains an attractive yet elusive approach for correcting inherited mutations and preventing subsequent diseases such as emphysema. In vivo gene transfer has been limited in many types of cells by inefficient gene delivery, as well as the limited life-span of differentiated cell types.
However, using mice, the BUSM researchers have discovered a way to deliver genes selectively to as many as 70 percent of a mouse lung’s alveolar macrophages (AM), a key cell type contributing to emphysema. Researchers applied this approach to achieve sustained in vivo expression of normal human alpha-1 antitrypsin (hAAT) protein levels capable of improving emphysema in mice. As a result, the lung macrophages carrying the therapeutic gene survived in the lung for a two-year lifetime following a single intra-tracheal injection of the engineered lentiviral vector.
"The progression of emphysema in mice exposed to elastase was significantly improved by the gene therapy as evidenced by improvements in lung compliance and alveolar size," said Dr. Andrew Wilson, lead author of the study and assistant professor of medicine at BUSM.
After 24 weeks of sustained gene expression, no humoral or cellular immune responses to the human hAAT protein were detected in the mice, challenging the idea that lung macrophages are short-lived and suggesting that these differentiated cells may be considered for in vivo gene therapy applications such as the sustained correction of hAAT deficiency. Click here to access the full story on ScienceDaily.